
Class 
Book 



COPYRIGHr DEPOSIT 



A GUIDE 



TO THE 



CLINICAL EXAMINATION 



OF 



THE BLOOD 



FOR DIAGNOSTIC PURPOSES 



BY 

RICHARD C. CABOT, M.D. 



WITH COLORED FLATUS AND ENGRAVINGS 



ffittb IRe^ise^ 3£^iticr> 



NEW YOEK 
WILLIAM WOOD AND COMPANY 

MDCCCCIV 



LIBRARY of CONGRESS 

Two GoDies Received 

APR 27 1904 

CoDyriffht Entry 

CLASS A- XXc. No. 

COPY B 



Copyright, 1904, 
By WILLIAM WOOD AND COMPANY. 



TO 

WILLIAM SIDNEY THAYEK, M.D., 

ASSOCIATE PROFESSOR OP MEDICINE IN JOHNS 
HOPKINS UNIVERSITY, 

IN GEATKFUL BECOGNITION OF THE STANDARD OP THOKOUGH 
WOEK ESTABLISHED BY HIM. 






PREFACE TO THE FIFTH EDITION. 



About ninety pages of new matter have been added and about 
twenty pages stricken out. The most important changes are due to 
the introduction of the " Romanowsky " staining method (Jenner, 
Leishman, and others), as applied to routine blood examination. 
A new set of colored plates has been prepared from specimens 
stained in this way. 

Considerable additions have been made to the chapters on In- 
fectious Diseases and Blood Parasites and minor changes on almost 
every page in the book. 

I am greatly indebted to Dr. Mary \Y. Rowley for her pains- 
taking and, I think, most successful work upon the colored plates. 

190 Marlboro Street. Boston, 
April 1st, 1904. 



TABLE OF CONTENTS. 



BOOK I. 
Introduction. 

PAGE 

Scope axd Value of Blood Examination, . . . . . .3 

PAPvT I. 

Methods of Clixical Examination of the Blood. 

CHAPTER I. 

I. Estimation of the Total Volume or Mass of Blood, .... 5 

II. Examination of the Fresh Blood, 7 

CHAPTER II. 

I. Counting the Corpuscles (Thoma-Zeiss Instruments), . . .13 

Counting the Red Corpuscles, 13 

Counting the White Corpuscles, 19 

Counting both Red and White Corpuscles with the Same Pipette, . 20 

II. Dui-liam's Modified Hsemocytometer, 23 

CHAPTER III. 

Other Methods op Examination, 25 

Oliver's Hsemocytometer, 25 

The HEematocrit, 28 

Haemoglobin Estimation, 30 

I. Tallqvist's Haemometer, 30 

II. Dare's Haemoglobinometer, ........ 31 

III. Oliver's Hsemoglobinometer, 33 

IV. V. Fleischl's Haemometer, . 34 



Vlll 



TABLE OF CONTENTS. 



Estimating the Specific Gravity, 

Study of the Finer Structures of the Blood, 

Bacteriological Examination, 

Other Methods of Examination, 



PAKT II. 

Physiology of the Blood, 



CHAPTER lY. 














Appearance or Fresh Normal Blood, 49 


I. Red Corpuscles, ,...., 








49 


11. White Cells, . . . . . . 








51 


III. Blood Plates, 








51 


IV. Fibrin Network, ...... 








52 


Average Diameter of Red Cells, . . . 








58 


Normal Number of the Red Cells, 








54 


Inthience of Menstruation, Parturition, Lactation. 








55 


Influence of Vasomotor Changes, 








55 


Influence of Nutrition, 








56 


Influence of the Seasons, 








56 


Influence of Fatigue, ...... 








56 


Influence of Age, 








56 


Normal Number of White Cells, 








56 


Normal Number of Blood Plates, 








57 


Mailer's "Blood Dust," . . . . 








58 


CHAPTER V. 


Finer Structure of the Blood 59 


Appearances of Dried and Stained Specimens. 








. 59 


Red Cells, 








. 59 


White Corpuscles, .... 










. 60 


Polymorphonuclear Neutrophiles, 










. 60 


Lymphocytes, .... 










. 61 


Eosinophiles, .... 










. 61 


Mast cells, 










. 62 


Terminology, 










. 62 


Normal Percentage of each Variety, . 










. 63 


Myelocytes, . . . . . 










. 64 


Eosinophilic Myelocytes, 










. 65 


Degenerated Leucocytes, 










. 66 


Transitional Neutrophiles, . 










66 


Tiirck's "Stimulation Forms," . 












66 



TABLE OF CONTENTS. 



IX 



PART III. 



General Pathology of the Blood. 



CHAPTER Vr. 

Unequal Distribution of the Blood — Polycythemia — Dilution 
AND Concentration of the Blood, 

1. Unequal Distribution, 

2. Local or Peripheral Polycytliaemia, 

(a) General Cyanosis, . 

(b) Local Cyanosis, 

3. Temporary Serous Plethora, . 

Polycythaemia, 
Concentration of the Blood, 
The Blood in High Altitudes, 
Phosphorus and CO Poisoning, 



PAGE 

68 



70 
70 
71 

74 
75 



CHAPTER VII. 



Anemia and Hydremia, .... 






. 76 


Anaemia, 




. 76 


Pallor and Anoemia, 




. 76 


"Tropical Anaemia," 




. 76 


Distinction between Primary and Secondary Anaemia, 




. 77 


Secondary Anaemia, 




. 78 


I. First Stage— Loss of Color, AVeight, and Size, 




. 78 


II. Second Stage — Poikilocytosis and Degeneration, 




. 78 


(a) Endoglobular Changes, .... 




. 79 


(b) Crenation and Poikilocytosis, 




. 79 


(c) Motility, ..... 






. 79 


(d) Oval Shape, .... 






. 80 


(e) Changes in Staining Properties, 






. 80 


III. Third Stage— Deglobularization, 






. 81 


IV. Nucleated Red Corpuscles, . 






. 82 


(a) Normoblasts, .... 






. 82 


(b) Megaloblasts, .... 






. 83 


(c) Microblasts, .... 






. 83 


(d) Atypical Forms, 






. 84 


Summary, . . . . . 




. 85 


Hydraemia, ....... 






= 86 



X TABLE OF CONTENTS. 

CHAPTER VIII. 

PAGE 

Leucocytosis — Lymphocytosis — Eosinophilia — Myelocytes, . . 88 

Definition of Leucocytosis, 88 

Physiological Leucocytoses, 90 

Diurnal Leucocytosis, 90 

Leucocj'tosis of the New-Born, 92 

Leucocytosis of Pregnancy, 93 

Leucocytosis after Parturition, 93 

Leucocytes in Puerperium, 93 

Leucocytosis from Exercise, Massage, and Cold Baths, . . 94 

Terminal Leucocytosis, 96 

Pathological Leucocytoses, 96 

Post-hemorrhagic Leucocytosis, 96 

Inflammatory Leucocytosis, 97 

Toxic Leucocytosis, 100 

Leucocytosis of Malignant Disease, 100 

Leucocytosis due to Therapeutic and Experimental Influences, 101 
Cell Structure of the Leucocytes in Leucocytosis, , . . 102 

Absence of Leucocytosis, 104 

Leucopenia, 104 

Lymphocytosis, 105 

Pertussis, 106 

Eosinophilia, 107 

Diminution in Eosinophiles, 110 

Diagnostic and Prognostic Value, Ill 

Myelocytes, m 

Mast cells, . ^^^2 



CHAPTER IX. 

General Pathology of the Blood as regards Hemoglobin, Fi- 
brin, LiPEMiA, Melanemia, and Hemorrhage, . . .113 

Haemoglobin and the "Color Index," , . 113 

Fibrin, . [ , . lU 

Lipaemia, ' ^^^ 

Melansemia, -.-.g 

Hemorrhage, * j-^g 

Changes in the Blood Resulting from Hemorrhage, '. '. ! 116 

Blood Regeneration, jji^ 

Regeneration of Red Cells, .....!! 118 

Blood Crisis, * j-^g 

Regeneration of White Cells, . . . . .* ] ng 

Chronic Hemorrhage, .... ' ' * ° 119 



TABLE OF CONTENTS. XI 

BOOK IL 
Special Pathology of the Blood. 

PAKT I. 

Diseases of the Blood. 
CHAPTER L 

PAGE 

The Primary Anemias, 123 

1. The Blood in Pernicious Anaemia, . . . . . . . 123 

1. Volume and Oxygen Capacity, . . . . 123-146 

2. Gross Appearances, . . 123 

Red Cells and Haemoglobin, . . . ... . 124 

White Cells, .127 

Haemoglobin, . 128 

Qualitative Changes, ........ 129 

1. Red Corpuscles, . . . . . . . . 129 

(a) Increase in Diameter, . . . . . . 129 

(b) Deformities in Shape, . . . . . . 130 

(c) Staining Properties, . . . . . . . 131 

2. Nucleated Red Corpuscles, ...... 132 

3. White Corpuscles, . . . . . . . . 135 

The Blood in Remissions, 138 

Characteristics of Pernicious Anaemia, Summary, . . . 140 

Diagnostic Value of Pernicious Anaemia, ..... 140 

1. Pernicious Anaemia and Chlorosis, . . . . . 140 

2. Pernicious Anaemia and Malignant Disease, . . . 140 

3. Pernicious Anaemia and other Secondary Anaemias, . 142 

4. Pernicious Anaemia and Leukaemia, 143 

Prognostic Value of the Blood in Pernicious Anaemia, . . 143 

2. Fatal Anaemia with Hypoplastic Marrow, 146 

3. The Blood in Chlorosis, 147 

The Blood in Gross 148 

Red Cells and Haemoglobin, . . . . . . 148 

Quantitative Changes, . . . . . . . 148 

Qualitative Changes, . . . . . . . 150 

Specific Gravity, 151 

White Cells 152 

Quantitative Changes, . 152 

Qualitative Changes, . . . . . . . 152 

Blood Regeneration in Chlorosis, ...... 153 

Chlorosis without Known Blood Changes, .... 153 

Summary and Diagnostic Value, 153 



Xll 



TABLE OF CONTENTS. 
CHAPTER IL 









PAGE 


Leukemia, 1'5'5 


I. Myeloid Leukaemia, .... 


. 156 


Red Cells, 


. 156 


Qualitative Changes, .... 




. 157 


White Cells, 




. 158 


Quantitative Changes, .... 




. 158 


Qualitative Changes, , . . . 




. 161 


1. Myelocytes, ... 


. 


. 161 


2. Polymorphonuclear Cells, . 






. 162 


3. Lymphocytes, 






. 163 


4. Eosinophiles, 




. 163 


5. Basophiles, 




. 164 


6. Mitoses, 




. 165 


7, Polymorphous Condition of the Blood, 




. 165 


8. Remissions, 




. 166 


II, Lymphsemia, 






. 166 


Red Cells, . 






. 167 


White Cells 






. 167 


Quantitative Changes, ... 






. 167 


Qualitative Changes, . . . . 






. 168 


Summary of Blood Changes in Leukaemia, 






. 171 


Differential Diagnosis of Leukgemic Blood, 






. 171 


Effect of Intercurrent Infections in Leukaemia, 






. 173 


Hodgkin's Disease, 






. 175 


The Blood, 






. 176 


White Cells, 






. 180 


Summary and Diagnostic Value, 






. 181 


Effects of Splenectomy on the Blood, . 






. 181 


"Splenic Anaemia," 






. 182 



PAET II. 

Acute Ixfectious Diseases. 

CHAPTER III. 

Influence op Fever on the Blood 186 

Pneumonia, 187 

(a) Bacteriology of the Blood, 187 

(&) Coagulation and Fibrin, 188 

(c) Concentration of the Blood, 188 

(d) Specific Gravity, 188 

Red Cells, . , 188 

White Cells, Corpuscles, . 189 

Qualitative Changes, . , 191 

Diagnosis and Prognosis, . 194 



TABLE OF CONTENTS. Xlll 

PAGE 

Broncho-Pneumonia, . . . , 195 

Typhoid Fever, 196 

Bacteriology of the Blood, . . . . . . . . 196 

Quantitative Changes, . 197 

Red Cells, . . .197 

Haemoglobin, 198 

Leucocytes, 199 

Complications, 201 

Qualitative Changes, 205 

Summary and Diagnostic Value, 207 

Dysentery, 209 

Diphtheria, . . . • 210 

Red Corpuscles, . . . . 210 

Haemoglobin, 211 

White Corpuscles, 211 

Summary, . . . . . . . . . . . 213 

CHAPTER IV. 

Acute Infectious Diseases (Continued). 

Scarlet Fever, . .215 

Red Cells, 215 

White Cells, 215 

Summary, 217 

Diagnostic Value, ......... 217 

Measles, Rothcln, and Mumps 219-220 

Whooping-Cough, 220 

Smallpox (Variola), 221 

Vaccination, 221 

Chickenpox, 223 

Acute Articular Rheumatism, 224 

Fibrin, Alkalinity, Red Cells, 224 

Qualitative Changes, Haemoglobin, Leucocytes, . . . 225 

Summary and Diagnostic Value, 230 

Asiatic Cholera, 231 

Erysipelas, 232 

Tonsillitis (Follicular), . 234 

Grippe, 236 

Septicaemia, 237 

Bactei-iology of the Blood, , . 237 

Red Cells, 239 

Leucocytes, 243 

Summary and Diagnostic Value, 245 

Appendicitis, 245 

Narcosis, Effect on Blood, 253 

Surgical Diseases, Blood in, 254 

Differential Diagnosis, . . 259 

Pus Tube, Pelvic Abscess, and Pelvic Peritonitis, .... 260 



XIV 



TABLE OF CONTENTS. 



PAGE 

Differential Diagnosis, 263 

Otitis Media, . ^^ 

Osteomyelitis, '^"'* 

Otlier Abscesses, ^"^ 

Diagnostic Value, *"' 

Gonorrhoea, . . . • '^^* 

Yellow Fever, 268 

Typhus Fever, 269 

Malta Fever, 269 

Glanders, 270 

The Bubonic Plague, . 271 



Actinomycosis, 



271 



Tetanus, 272 

Rabies, 272 

Beri-beri, 273 

Relapsing Fever, 274 



CHAPTER V. 

Diseases Affecting the Serous Membranes, 
Serous Pleurisy, 

Summary and Diagnostic Value, 

Purulent Pleurisy (Empyema), 
Peritonitis, 

Diagnostic Value, 
Pericarditis (with Effusion), 
Meningitis, ...... 

Epidemic Cerebro-Spinal Meningitis, 

Diagnostic Value, 



275 
275 

277 

278 
280 
282 
282 
284 
286 
287 



PART III. 
Chronic Infectious Diseases. 



CHAPTER VI. 



Tuberculosis, 

Red Corpuscles and Haemoglobin, 
{a) Quantitative Changes, 
(b) Qualitative Changes, 

Leucocytes, 

Changes in Phthisis, 
Changes in Bone Tuberculosis, 
Changes in Acute Miliary Tuberculosis, 
Changes in Tuberculous Peritonitis, 
Changes in Tuberculous Meningitis, 
Changes in Tuberculous Pericarditis, , 
Changes in Tuberculous Pleurisy, 



288 
288 
288 
290 
291 
291 
294 
297 
301 
303 
306 
306 



TABLE OF CONTENTS. 



XV 



PAGE 

Changes in Glandular Tuberculosis, 306 

Changes in Genito-Urinary Tuberculosis, .... 307 

Syphilis, .308 

Changes in Red Ceils and Haemoglobin, 308 

Justus' Reaction, . . . , 310 

Changes in White Cells, . . . . . . . . 311 

Diagnostic Value, 312 

Leprosy, 313 

PAET lY. 

Diseases of Special Organs. 



CHAPTER VII. 

Diseases of the Digestive Apparatus, 
Diseases of the Stomach, . . . 

Anorexia Nervosa, .... 

Gastric Ulcer, 

Acute Gastritis and Dyspepsia, . 

Chronic Gastritis, .... 

Hyperacidity and Hypersecretion, 

Dilated Stomach, .... 

Corrosive Gastritis, .... 
Diseases of the Intestine, .... 

Influence of Saline Cathartics on the Blood, 

Acute Enteritis, 

Dysentery, 

Chnmic Diarrhoea, .... 

Intestinal Obstruction, 
Diseases of the Liver, .... 

Catarrhal Jaundice, .... 

Qualitative Changes of Red Cells, 

Summary and Diagnostic Value, 

Cirrhosis of the Liver, .... 

1. Ordinary (Atrophic) Cirrhosis without Jaundice 

Qualitative Changes, 
Haemoglobin, .... 
White Cells, .... 

2. Hypertrophic Cirrhosis with Jaundice 

Red Cells and Haemoglobin, . 

White Cells, .... 

Diagnostic Value, . 
Hydatid Cyst of tbe Liver, 
Acute Yellow Atrophy of the Liver, . 
Phosphorus Poisoning, 

Cholaemia, 

Cholelithiasis, 



315 
316 
316 
316 
322 
324 
324 
325 
326 
326 
326 
326 
327 
328 
329 
330 
330 
332 
332 
332 
332 
333 
334 
335 
335 
336 
337 
337 
337 
339 
339 
339 
340 



XVI 



TABLE OF CONTENTS. 



Cholangitis, 
Abscess of the Liver, 
Caucer of the Liver, 
Gumma of the Liver, . 
Hemorrhagic Pancreatitis, . 
Diseases Affecting the Heart, 
Pericarditis, 
Endocarditis, 
Ulcerative Endocarditis, 

Red Cells, 

White Cells, . 

Diagnostic Value, . 
Myocarditis, 
Valvular Heart Disease, 

White Cells, . 
Congenital Heart Disease, 
Aneurism, 
Diseases of the Kidneys, 
Acute Nephritis, . 

Red Cells i^nd Haemoglobin, 

White Cells, . 
Chronic Diffuse and Chronic Parenchymatous Nephrit 

Red Cells and Haemoglobin, , 

Uraemia, 
Chronic Interstitial Nephritis, 
Pyelo-nephritis (Surgical Kidney) 
Nephrolithiasis, 

Diagnostic Value, 
Floating Kidney, . 
Pyonephrosis, 
Diseases of the Lungs, 
Bronchitis, 

Acute Bronchitis, 

Chronic Bronchitis, 
Emphysema and Asthma, 
Syphilis of the Lung, . 



PAGE 

. 342 
. 343 
. 345 
. 345 
. 345 
. 346 
. 346 
. 346 
. 346 
. 347 
. 347 
. 353 
. 352 
. 353 
. 354 
. 355 
. 360 
. 360 
. 361 
. 361 
. 363 
. 364 
. 364 
. 369 
. 369 
. 371 
. 371 
. 372 
. 372 
. 373 
. 373 
. 373 
. 374 
. 375 
. 376 
. 379 



PART y. 

Diseases of the Nervous System, Coxstitutioxal Diseases^ 
AND Hemorrhagic Diseases. 

CHAPTER VIIL 

Diseases op the Nervous System, 381 

Neuritis, 381 

Cerebral Tumor, ... . 383 



TABLE OF CONTENTS. XVll 

PAGE 

Diseases of the Brain, 383 

Cerebral Hemorrhage, 385 

Chorea and Tetany, 387 

Diseases of the Spinal Cord, 387 

General Paralj^sis of the Insane, 388 

Hystei'ia and Neurasthenia : Hypochondriasis, 389 

Mental Diseases, 390 

Constitutional Diseases, 391 

Obesity, 391 

Diabetes, 391 

Eed Cells, 393 

White Cells, 393 

Gout, 393 

Myxoedema, 394 

Cretinism, 396 

Graves' Disease, ; . . . 396 

Addison's Disease, 398 

Diseases of Bone, 399 

Arthritis, 399 

Fracture, 400 

Osteomalacia, 400 

Rickets, 401 

Red Cells, 402 

White Cells, 402 

Qualitative Changes, ......... 402 

CHAPTER IX. 

Blood Destruction and Hemorrhagic Diseases, .... 403 

Purpura Hsemorrhagica, 403 

Scurvy and Barlow's Disease, 404-405 

Haemolysis, 405 

Haemophilia, 405 

Haemoglobinaemia in Infectious Diseases, 406 

Paroxysmal Hsemoglobinaemia, . . . . . . . 407 

Burns, Snake Poison, etc., 407-408 

MethaemoglobinEemia, . . 408 

Poisons, Chlorate of Potash, Antipyretics, etc., . . . 408-410 

Illuminating Gas, 412 

Tansy Poisoning, 415 

Corrosive Poisoning, 415 

Opium Poisoning, . 415 

Suffocation by Smoke, 416 

Ptomain Poisoning, 417 

Acute Alcoholism, 417 

Plumbism, 419 

Mercurial Poisoning, . . 419 

Sunstroke and Heat Exhaustion, . . . . . . 431 



xviii TABLE OF CONTENTS. 



PART VI. 

Malignant Disease, Blood Parasites, and Intestinal 
Parasites. 

CHAPTER X. 

PAGE 

Malignant Disease, . . , . 423 

The Blood as a Whole, 423 

Cancer, 423 

Red Cells, 423 

Haemoglobin, 425 

Regeneration of Blood after Operations on Cancerous 

Growths, 425 

Qualitative Changes in Red Cells, 427 

White Cells, ... 428 

Quantitative Changes, 428 

Influence of Position and Size of Tumor, .... 429 

Influence of Individual Constitution, 430 

In Cancer of the Breast, 432 

In Cancer of the Stomach, 433 

Digestive Leucocytosis in Gastric Cancer, .... 436 
Effect of Metastases in Gastric Cancer .... 438 

In Cancer of the Gullet, 439 

In Cancer of the Liver, 440 

In Cancer of the Intestine, 443 

In Cancer of Omentum and Abdominal Organs Generall}', . 445 

In Cancer of the Kidney, 446 

In Cancer of the Uterus, 447 

In Cancer of other Organs 448 

Qualitative Changes in the Leucocytes, 450 

Sarcoma, 452 

Red Cells, 453 

Haemoglobin, 453 

White Cells, 453 

Qualitative Changes of Leucocytes, 457 

Summary, , 459 

Diagnostic Value, 459 

CHAPTER XI. 

Blood Parasites, . 462 

Examination for the Plasmodium Malariae and Its Products, . . 462 

Time for Examination, 462 

Method of Examination, 462 

The Malarial Organism in Fresh Specimens, .... 464 

The Malarial Organism in Stained Specimens, . . ... 465 



TABLE OF CONTENTS. XIX 

PAGE 

Comparison of Tertian and vEstivo-Autumnal Rings, . . 466 

Tertian Parasite ; Later Stages, 466 

^stivo-autumnal Parasites, 467 

Quartan Parasites, 468 

Flagellate Bodies, .468 

Other Changes in the Blood, . , 470 

Red Corpuscles, 470 

Haemoglobin, . . . 471 

White Cells, 472 

Malarial Hsemoglobinaemia, 473' 

Typhoid Fever and Malaria, 473' 

CHAPTER Xn. 

Diseases due to Animal Parasites, 474 

Filaria Sanguinis Hominis, . . . . . ' . . . . 474 

Spirochaete of Relapsing Fever, 481 

Technique of Examination, 485 

Spotted Fever (Tick Fever), 485 

Distomum Haematobium, 486 

Bilharzia Disease, 486 

Trypanosomiasis, . 487 

Anaemia due to Intestinal Parasites, 488 

Bothriocephalus Anaemia, 489 

Ankylostomiasis (Uncinariasis), 490 

The Blood in Gross, 491 

Trichiniasis, 497 

Summary and Diagnostic Value, 503; 

Strongyloides Intestinalis, 502 

Taenia, 504 

Tricocephalus, 504 

Amoebic Dysentery, 504 

CHAPTER XIII. 

Diseases op the Skin, 505 

Dermatitis Herpetiformis, 505 

Herpes Zoster, . 506 

Herpes Tonsurans, 506 

Chronic Eczema, 507 

Scleroderma, . . . 507 

Psoriasis, 507 

Pemphigus, 508 

Lupus, 508 

Drug Eruptions, . . . 508 

Other Dermatoses, 509- 



XX 



TABLE OF CONTENTS. 



CHAPTER XI 7 



The Blood in Infancy, .... 
Premature Infants, . . . , 
General Characteristics, 
Summer Diarrhoeas of Infancy, . 
The Anaemias of Infancy, 

Classification, .... 

Secondary Anaemias, 

Qualitative Changes, 

" Anaemia Infantum Pseudoleuksemica. 
Importance of the Term, 

Pernicious Anaemia in Infanc}', 

Polymorphous Condition, 

Leukaemia in Infancy, . 



PAGE 

. 510 
. 510 
. 510 
. 513 
. 513 
. 514 
. 514 
. 516 
. 519 
. 520 
. 524 
. 526 
. 526 



PART VII. 
Examination of the Serum. 



CHAPTER XV. 

Fourteen Types of Serum Reaction, 528 

The Widal Reaction in Typhoid, 529 

General Description, 529 

Technique, 531 

The Body Fluids Used, 531 

Use of the Whole Blood— Fluid, 531 

Use of the Whole Blood— Dried, 532 

Use of the Fluid Serum, 533 

The Cultures of Typhoid Bacilli to be Used, .... 533 
The Use of Suspensions instead of Cultures, .... 534 

The Use of Attenuated Cultures, 534 

Dilution and the Time Limit, 534 

The Microscopical Examination, 535 

How Early does the Reaction Appear? 536 

How Late does the Reaction Last? 536 

The Intensity of the Reaction, 536 

Control Cases, 537 

Summary of Clinical Evidence 537 

Sero-Diagnosis of Other Diseases, 537 

Cholera, 537 

Malta Fever, . 538 

The Bubonic Plague, 538 

Dysentery, 539 

Bibliography, ........... 541 

Index, 545 



BOOK I. 



INTRODUCTION. 



SCOPE AND VALUE OF BLOOD EXAMINATION. 

HEMATOLOGY has now established for itself a definite field of 
usefulness in the practice of medicine. It has solved some prob- 
lems where least was hoped from it, and given us disappointingly 
little help where great expectations had been aroused. We might 
have expected from it some light on the nature of rheumatism, fu- 
runculosis, uraemia, diabetes, but none has come. 

On the other hand, who could have hoped that it would help us 
in the diagnosis of central pneumonia, of deep-seated suppurations, 
and of trichinosis, or in the prognosis of relapsing fever or of pneu- 
monia? 

There are probably not more tnan five or six diseases in which 
the blood examination gives us the diagnosis ready-made, but there 
is a very considerable number of conditions in which the blood ex- 
amination will help us to make it. Not pathognomonic signs, but 
links in a chain of evidence are what we are to expect from blood 
examination. Very often the simple discovery that the blood is- 
normal may be a fact of the greatest value in diagnosis. 

On the whole it seems to me that the examination of the blood 
gives evidence similar in kind and not much inferior in value to 
that obtained by examination of the urine. Both methods of ex- 
amination give us (a) a ready-made diagnosis in a few diseases ; (h) 
side lights on a good many obscure conditions; and (c) the fre- 
quently great assistance of a negative report. In certain wards of 
the Massachusetts General Hospital it has been for some years the 
rule to examine the blood of every patient as a matter of routine 
at the time of entrance. In a small proportion of cases this gave 
negative evidence only ; in a much larger proportion it materially 
assisted in the making of a diagnosis. 

Improvements in technique have lessened the labor and increased 
the accuracy of blood examination. The most important facts 



4 INTRODUCTION. 

about the blood of nearly every case can be obtained by a practised 
observer in fifteen minutes. 

The blood is the only tissue that we can study easily during the 
life of the patient. Its relations to all other tissues are such that 
it is typical of them all in a way that no other tissue is, acting (jii 
all and being acted on by all. As yet we have studied chiefly its 
morphology, and from that single aspect obtained most of the clini- 
cally valuable information which we possess about it. But the 
field of the blood chemistry is in many respects even more promis- 
ing at the present time, and there seems reason to believe that the 
study of the blood is still in its infancy and will take a higher place 
in the future as aa aid to diagnosis, prognosis, and treatment. 

Like all methods of physical examination it has especial useful- 
ness when Ave cannot communicate with a patient, either by reason of 
his unconsciousness, stupidity, or insanity, or because he speaks no 
widely used language. In such cases the detection of marked anae- 
mia, leucocytosis, eosinophilia, a typhoid serum reaction, or a mal- 
arial organism may be of great assistance. Malingering is made 
more difficult by it, and in the differentiation of organic from func- 
tional disease it is often very helpful. There is no febrile disease 
on which it may not throw light. 

The evidence for these and many other aids furnished b}^ the 
blood examination in clinical work is given in the later chapters of 
this work. 



PART I. 

METHODS OF CLINICAL EXAMINATION OF 
THE BLOOD. 



CHAPTEE I. 



CoxFixiNG ourselves to the clinically available processes by 
which we can gain information of diagnostic or prognostic value, 
blood examination at the present time embraces the following proc- 
esses. 

1. Estimation of the total volume of the blood and of its oxygen 
capacity. 

2. Examination of the fresh blood (with or without a warm 
stage). 

3. Counting the red and the white corpuscles. 

4 Estimation of the amount of coloring matter. 

5. Examination of dried and stained specimens. 

6. Bacteriological examination of the blood. 

7. Examination of the serum. ^ 

8. Estimation of the coagulation time. 
Less important are : 

9. Estimation of volume of corpuscles and of plasma in a given 
quantity of blood. 

10. Estunation of the specific gravity of the blood. 

11. Estimation of the number of blood plates. 

12. Estimation of the amount of fibrin. 

To describe these processes in detail is the purpose of the next 
chapters. 

I. Estimation of the Total Volume or Mass of Blood. 

Until recent years the determination of the total mass of the 
blood has been practically beyond our reach, and our blood exami- 
nations have dealt wholly with small " samples " draAvn from the 
" See Chapter xiii. of Book II. 



6 CLINICAL BLOOD EXAMINATION. 

j)eriplier}- and treated as typical of the rest without regard to any 
possible variations in the total amount of blood in the vessels. 

But recently Haldane and Smith, in three important and inter- 
esting papers,' have suggested and applied a method which, if it 
stands the test of time and criticism, will add very materially to 
our knowledge of blood physiology and blood pathology. 

The essential features of their method are as follows : 

1. The patient inhales a measured volume of CO (a harmless 
and not unpleasant process). After two or three minutes a ft-w 
drops of blood are taken for analysis and the percentage to which 
the haemoglobin has become saturated with carbonic oxide is esti- 
mated (by the carmine method, see reference at foot of page) . 

2. Knowing the amount of CO inhaled, and the degree in which 
the blood has become saturated by this known amount, the quantity 
of CO capable of being taken up by the whole of that patient's 
blood can be calculated. Thus, supposing that the volume of car- 
bonic oxide delivered was 150 c.c, and that the blood was twenty- 
live per cent saturated, it is obvious that the blood would have bt^en 
one hundred per cent saturated by 600 c.c. Its total capacity 
for CO (or for oxygen) is 600 c.c. 

3. HoAv then shall we connect this estimate of total nxijtii'n 
capacitij with the roJume of the blood ? In a previous research the 
writers showed that the oxygen capacity per 100 c.c. of any given 
sample of blood can be accurately estimated by comparing its color 
with the color of an equal sample of ox blood whose capacity for 
oxygen has been previoush' determined. For example, a patient 
having absorbed 100 c.c. of CO, it is found that his blood is one-fifth 
saturated by this gas. The total capacity for CO (and so for oxy- 
gen) is therefore 500 c.c. But further, the patient's blood is found 
to have the same color as an ox's blood every 100 c.c. of which 
has been previously determined to be capable of taking up 20 c.c. 
of oxygen. The patient's total oxygen capacity (500 c.c.) divided 
by the oxygen capacity of ever}^ 100 c.c. of his blood (20) gives us 
25. This figure is then the number of hundreds of cubic centi- 
metres of blood in his body — 2,500. 

Smith has now applied this method to over one hundred cases, 
and found it to produce no appreciable ill-eifects on the patient. 
As the result of these studies, he estimates the average volume of 

' 1. Journal of Physiology, xxii., p. 232. 2. Journal of Physiology, 
XXV., p. 331. 3. Transactions of the Pathological Society. 1900. vol. li. 



METHODS OF CLINICAL EXA3IIXATI0N. 7 

blood in health as 3,240 c.c. or 3,420 gm. The latter figure is 
obtained by means of the average specific gravity of normal blood 
(taken as 1.055). In the fourteen normal cases studied the blood 
mass varied from 2,830 to 4,550 gm. or -^^ to J-^- the body weight, 
but was never as large as had previously been estimated (^V)- 

In chlorosis, Smith found that the ajDparent diminution in hte- 
moglobin was, in fact, due to the great increase in the plasma of 
the blood (serous plethora), the total oxygen capacity or hsemoglobin 
remaining normal. In j^^i^nicious anaemia, on the other hand, the 
amount of plasma is sometimes increased and sometimes dimin- 
ished, but the oxygen capacity or hsemoglobin is always low. These 
observations will be referred to again later (see page 123). 

II. EXAMIXATIOX OF THE FkESH BlOOD. 

(a) Puncture. — In all the processes about to be described (ex- 
cept the bacteriological examination) the first step is as follows : 

Gently cleanse the lobe of the patient's ear with a damp cloth 
and then dry it. All ^dgorous rubbing or kneading is to be avoided. 
Attempts to sterilize the skin or to cleanse it with alcohol and ether 
are a waste of time. A small lancet or a bayonet-pointed surgical 
needle may be used : a sewing needle gives more pain and draws less 
blood from a given depth of puncture. A steel pen, with one nib 
broken off, makes a good lancet. The needle need not be sterile. 
In several thousand blood counts made at the Massachusetts Gen- 
eral Hospital since 1893 the needles have never been sterilized and 
no signs of sepsis have been seen in any case. 

Possibly this is due in part to the fact that the next ste^) in the 
process after the puncture has been made is always to wipe away 
four or five successive drops as they emerge. This serves not only 
to get the blood flowing freely, but also to wash the ear in its own 
blood. 

The puncture is best made into the lower surface or edge of the 
lobe, which is steadied with the fingers of the left hand. A very 
quick stroke gives least pain, the hand rebounding like a piano 
hammer. If the skin of the lobe is stretched tight Avith the fingers 
of the left hand so that no "give '' is possible, the quick puncture 
gives hardly any pain. I have repeatedly taken blood from a 
sleeping child without waking it. What hurts the patient is the 
mistaken tenderness that slowly jji-esses the needle through the skin. 



8 CLINICAL BLOOD EXAMINATION. 

The puncture must be deep enough to make the blood flow freely 
and without strong pressure, after it is once started by pressing out 
a few drops. Blood squeezed out with strong pressure should never 
be used for counting, as it may be considerably diluted with fluid 
from the neighboring tissues.' If the skin is moderately thin and 
the ear easily made hyperaemic, a puncture one-eighth of an incli 
deep is sufficient. With thick, bloodless skin it may be necessary 
to go in one-quarter or one-third of an inch — never more. Beware 
of bleeders. I have seen bleeding from a puncture made for a blood 
count which could not be checked for three-quarters of an hour. 
It is always safer to ask after a history of haemophilia as a matter 
of routine before taking blood, just as one asks after false teeth be- 
fore etherizing. If there is a history of haemophilia, a mere touch 
of the needle point will give us all the blood we need without em- 
barrassing us with a troublesome hemorrhage. 

There is no question as to the superiority of the ear over tlie 
finger for drawing the drop. The ear is less sensitive than the 
finger, and a slighter puncture gives us all the blood we need. 
Moreover, it is a distinct advantage, especially in children, that the 
patient cannot watch the puncture of the ear, or the preparations 
for making it, and cannot easily withdraw the part. A sleeping 
patient often needs to be roused to get at his finger, while his ear is 
usually easily accessible above the bed clothes. Again, the absence 
of any bony prominence against which to press makes us less likely 
to use too much pressure than if we puncture the finger. 

When one is making frequent examinations of the blood of a 
sensitive person, as in pneumonia, these details are of real impor- 
tance, and in cases of pernicious anaemia in which the previous 
attempts to get blood from the finger had been absolute failures, I 
have found no difficulty in getting it from the ear. In this disease 
the advantages of the ear over the finger are peculiarly great. 

Preparation of Temporary Specimens for Immediate Examination. 

(h) When, after wiping away the first four or five drops, a good- 
sized drop exudes spontaneously, touch the centre of a perfectly 
clean cover-glass against the summit of the drop without touchiwj 
the skin itself at all, and drop the cover-glass face downward upon 
a slide so that the force of the impact will help to spread the drop 
of blood thinly and evenly between slide and cover. It is recom- 
^ Moderate pressnre produces no error of importance. 




METHODS OF CLINICAL EXAMINATION. 9 

mended by Ehrlich and others to hold the cover-glass with forceps, 
but there is no harm in holding it with the fingers, provided we avoid 
touching either of its surfaces, i.e , hold it always as in Fig 1/ 

Slide and cover must be perfectly clean, else the blood will not 
spread out in a layer thin enough to avoid the corpuscles overlying 
each other so that not one of them is 
clearly seen. Further, as dirt simulates 
fairly closely some of the pathological ap- 
pearances for which we are on the look- 
out, its presence on the slide leads to loss 
of time or to mistaken conclusions. Cover- 
glasses, as they come from the shops, may 
be coated with a substance not easily to 
be removed. To get them really clean fig- i--Proper Method of Hold- 

° *^ ing a Cover-glass. 

nothing is so simple as or more effective 

than soap and water. After several years' use of the method 
of cleaning usually advised (viz., strong mineral acid, followed 
by alcohol and then by ether), I have become converted to the 
use of plain soap and water as the best and simplest way of 
cleaning slides or cover-glasses. Kub soap over every part of the 
glass, wash it off with water, and polish thoroughly with a clean 
handkerchief (most towels are apt to leave a scrap of lint on the 
glass).* If slide and cover are perfectly clean, are held as in Fig. 
1, and allowed to touch only the summit of the blood drop and not 
the skin, the blood will spread out properly between them, and no 
j^ressure on the cover-glass will be needed to make the layer of cor- 
puscles thin enough. Pressure is undesirable, as it often makes all 
sorts of artefacts in the preparation and hastens crenation of the 
red corpuscles. Better results are obtained if slide and cover are 
loarmed just before using, and it is well to have an assistant rub the 
slide vigorously with a towel just before it is used. 

This method is, of course, applicable only to specimens to be 

' I am not unmindful of Ehrlich's warning that the moisture of the fingers 
spoils the specimen ; but in practice I do not find it to be true except as re- 
gards the margin of the film, the good preservation of which is not essential. 
Only the thinnest cover-glasses in the market should be used, | inch is the 
best size. 

'^Further experience has convinced me that water alone is generall}^ suffi 
cient, provided the polishing, which is the chief factor of success, is thorough. 
Tissue paper is very useful for polishing cover-glasses. After pohshing, it is 
well to pass them through a Buuseu or alcohol llame once or twice. 



10 CLINICAL BLOOD EXAMINATION. 

immediately examined. Specimens which are to be transported or 
preserved should be prepared as directed on page 39. 

Prevention of CaU-Dpath. 

Slides so prepared are usually best examined with a one-twelfth 
oil-immersion lens. As a rule they keep long enough for jjurposes 
of examination without any further precautions, but if we desire to 
keep the blood fresh and uncoagulated for a longer period, it is best 
to exclude air in this way: Paint upon the slide with vaseline, 
cedar oil, or any gummy substance a hollow square or ring of about 
the size of the cover-glass, so that when the latter with its drop of 
blood is put down upon the slide the drop will spread out inside the 
ring of oil, which seals the margins of the cover-glass to the slide. 
Specimens so prepared will keep for many hours unchanged, and 
without crenation or coagulation, if the weather is warm or if the 
slide be kept in a warm place. 

In examining blood suspected of containing malarial parasites it 
is sometimes useful to put the whole microscope into one of the 
warming apparatuses devised for the purpose. This is better than 
any of the various kinds of warm stage in use, but in clinical work 
there is rarely if ever any need for artificial heating apparatus of 
any kind, provided the room and the slide are warm. 

WJiaf Can he Learned from Fresh Blood, 

In the first place we note the readiness or sluggishness of its 
flow from a puncture of standard depth. The blood flows more 
readily than usual in the following conditions : 

1 Peripheral congestion or vaso-dilatation. 

2= Exaggerated fluidity of the blood (chlorosis, some types of 
anaemia, and haemophilia). 

It flows sluggishly : 

1. After profuse hemorrhage or serous drain (cholera). 

2. In certain cases of extreme anaemia — e y. , emaciated cancer 
cases. 

3. Vasomotor spasm (cold, hysteria, Kaynaud's disease, uraemia 
^certain cases). 

4. Exaggerated coagulability 

Examination of the fresh blood by the method described above 



METHODS OF CLINICAL EXAMINATION. 11 

is also a good wa}' for ascertaining tlie presence or absence 
of— 

1. The Plasmodium malaria? 

2. The Spirocha^te of relapsing fever 

3. The Filaria sanguinis honiinis and the Trypanosoma. 

4. Eouleaiix formation among the red cells. 

It is also a quick and convenient method of finding out with ap- 
proximate accuracy : 

(a) Whether the blood contains an increased amount of fibrin ; 

(b) Whether any considerable anoemia or leucocytosis^ is present ; 

(c) Whether or not the amount of haemoglobin in the red cells 
is much decreased; 

(d) Whether the red corpuscles are deformed ; 

(e) Whether the "blood plates " are increased or not. A prac- 
tised observer can also make a diagnosis of leukaemia by this method 
in most cases, but here mistakes may easily occur. 

So much can sometimes be learned from a specimen prepared in 
this very quick and easy way that it should be as much a matter of 
routine as a urine examination. But in order to get any information 
from such a preparation Ave must previously have familiarized our- 
selves with the appearance of normal blood under such conditions — 
with the size, shape, color, and refractions of the red cells, white 
cells, and blood plates and their ratio to one another, and with the 
great variety of curious phenomena to be seen as a drop of blood 
gradually dries up between slide and cover. No book can teach 
this ; it must be learned by actual experiment. 

Some of the commoner sources of error will be referred to later. 
Here I will mention only the Brownian movement in the protoplasm 
of the corpuscles, to be distinguished clearly both from the amoeboid 
movements of the leucocytes or of the malarial parasite and also 
from the irregular contractions of the dying protoplasm, which give 
rise to pseudo- amoeboid motions in the crenated points of normal 
red cells or in the irregular projections of corpuscles deformed by 
disease (vide infra). 

For a more detailed description of normal red corpuscles, white 
corpuscles, and blood plates the reader is referred to Part II. 

An account of the pathological changes to be observed in the 
fresh blood will be given in later chapters. 

' More accuratel}^ it is only the ratio of red to white corpuscles that we 
can determine, and when the red are very much diminished in number we 
may be deceived into supposing that the white are increased. 



CHAPTEK II. 

COUNTING THE CORPUSCLES. 



I. The Thoma-Zeiss counter. 

II. Durham's modified counter. 

I. Out of the many instruments devised for this purpose that of 
Thoma-Zeiss with Zappert's modified ruling of the counting 

chamber is the best, and much 
the most commonly used.^ In 
the use of this instrument there 
are five steps or stages : 

1. Puncturing the ear. 

2. Diluting and mixing the 
blood thus obtained. 

o. Adjusting a drop of di- 
luted blood in the counting 
chamber. 

4. Counting the corpuscles. 

5. Cleaning the pipette. 

To count the white corpus- 
cles, an instrument different 
from that employed for the red 
is often used. 

The technique is nearly the 
same for both instruments, but 
for clearness' sake I shall de- 
scribe them separately. To 
save time I shall call the small- 
bore pipette used for red cor- 
puscles (Fig. 2, A) the "red 
counter," and the large -bore 



m 



pipette (Fii 
counter." 



Fig. 2.— Thoma-Zeiss Pipettes. A. For red cor- 
puscles ; B, for wMte corpuscles. 

^ The various modifications introduced fi-om time 
me to present advantages sufficient to make tliem 
ori2:inal instrument. 



B) the "white 



to time do not seem to 
deserve to displace the 




COUNTING THE CORPUSCLES. 13 

Counting the Red Corpuscles. 

{a) After puncturing the ear as above described, and as soon as 
the blood is flowing freely, put the point of the " red counter " into 
the drop as it emerges from the ear, and by sucking gently on the 
rubber tube attached to the other end, draw up blood to the mark 
0.5 on the pipette. It is convenient to rest 

the end of the pipette on the thumb as „, 

shown in Fig. 3. It needs some practice ^^-nSiI 

to stop exactly at the mark, but if we hap- 
pen to draw the blood up a little past the 
mark 0.5 no considerable error results, pro- 
vided we draw the column down again to 
the mark by tapping the point of the pipette 
on a towel, and provided also that the in- ^ 

strument is perfectly clean and dry. The ^^^^ /^ /fJ 
aiin and intention, however, should always fig. 3.— Method of Resting Point 
be to stop exactly at the mark 0.5, and with '^^ ^^p^"^ on the Thumb while 

^ -^ ' Sucking m Blood. 

a little practice we can do it, except with 

nervous or delirious patients, and those who carelessly move the 

head just at the critical moment. With such patients we usually 

have to content ourselves with drawing the blood a little beyond 

the mark 0.5 and then drawing it down again to the mark as above 

described. 

Diluting the Blood. 

(h) The bottle of solution to be used for diluting the blood 
should be ready uncorked at the bedside. Of the many solutions 
suggested by various authors none is better than Gower^ s^ the for- 
mula for which is as follows : 

Sodii snlpliat gr. 112 

Acid, acet 3 v. 

Aquse § iv. 

Toisson's solution is also very useful and stains the white cor- 
puscles so that they can be easily distinguished from the red. Its 
comj)osition is as follows : 

Methyl violet, 5 B 0.025 gm. 

Sod. chlor 1.000 " 

Sod. sulph 8.000 " 

Neutral glyceriu 30.000 cm. 

Aqua? destill 160.000 " 



14 CLINICAL BLOOD EXAMINATION. 

We must wait about ten minutes after mixing before the leucocytes 
are fully stained. Except for this delay, the only objection to this 
solution is that it is rather difficult to clean the pipette after usin;,' 
it. If the white cells are counted with another pipette the staining 
fluid can be as well dispensed with. 

Into a bottle of one of these solutions, ready at the bedside, tlit- 
point of the pipette is to be plunged as soon as the blood has been 
drawn up to the point O.o and the outside of the pipette wiped Qlean 
of blood. Suction is then exerted through the rubber tube the in- 
stant the point of the pipette is below the surface of the diluting 
solution. This suction is continued until the diluted blood has 
filled the bulb of the pipette and gone past it up to the point 
marked 101. It is not difficult to stop at this point, provided the 
pipette is perfectly clean and dry inside. Otherwise it is impos- 
sible. Should any mishap occur at this point, the whole process 
must be begun over again after carefully cleaning and drying the 
pipette. If no accident happens and the mixture is sucked up to 
and not past the mark 101, we have diluted the blood with two 
hundred times its bulk of neutral solution. If, instead of drawing 
the blood up to the mark 0.5, we draw it as far as the point marked 
1, and then dilute as above described, the mixture will be 1 to 100. 
Some observers habitually use this dilution. The objections to it 
are (1) That if the blood is accidentally drawn up too far (/.''., 
past the mark 1) we cannot draw it down again but must painfully 
clean and dry out the pipette (see page 18) and repeat the proc- 
ess. (2) If the blood contain approximately the normal number 
of corpuscles, they will be so crowded when adjusted on the ruled 
surface of the disc A that it is more difficult to count them. If we 
use another pipette for the white corpuscles, the dilution of 1 : 100 
has no advantage to coimterbalance these drawbacks. 

While sucking in the diluting solution, it is well to roll the 
pipette on the long axis with the fingers of the hand which holds it 
in the diluting fluid. This mixes the blood instantly and prevents 
any of it from floating on the top of the solution and thereby com- 
ing up undiluted into the narrow portion above the bulb of the 
pipette, where it might possibly escape thorough mixings- 
Next we thoroughly mix the blood and diluting fluid by shaking 
and rolling the pipette, its ends being closed by the fingers. The 

^ Care must be taken that uo saliva finds its wa}' through the rubber tube 
and into the pipette. Xever blow through the rubber tube. 



COUNTING THE CORPUSCLES. 1^ 

little glass ball within the bulb helps this process materially. A 
minute's brisk rolling and shaking is as good as live minutes', as I 
have convinced myself by many experiments, and the distribution 
of the corpuscles throughout the mixture is very even, provided 
there is no delay in proceeding to the next step,' viz. : 

(e) Adjusting a Drop of Diluted Blood in the Counting Chamher. 
— Remove the rubber tube from the pipette and blow out the por- 
tion of diluting solution which last entered the pipette, and which 
consequently has not been thoroughly mixed with the blood in the 
bulb. Five or six drops should be blown out before any is used for 

B 

. ^ 

A C 

Fig. 4.— Thoma-Zeiss Counting: Slide. A, Ruled disc ; B, cover-glass ; C, moat. 

examination. Next, put upon the surface of the counter (A, Fig. 4) 
a drop of such size that when the cover-glass (B) is let down over it, 
the whole of the disc A is covered with the drop without any being 
spilled into the " moat " (C) around it. Just how large such a drop 
should be, can be learned only by practice. It is not literally 
necessary that exactly the whole disc A should be covered, provided 
nine-tenths of it is covered, but any spilling over into the " moat " 
(C) entails serious error. ^ 

After the cover-glass has been let down upon the drop, we should 
be able (provided the whole instrument is clean) to see concentric 
rainbow rings between the cover-glass and the body of the instrument. 
These are known as Newton's rings. A little pressure with a needle 
on the cover-glass will often bring them out if they do not at once 
appear, but they must remain visible after the pressure is taken off. 
Otherwise we know that there must be some dirt or dust under the 
cover-glass preventing its settling exactly into position, and this will 
cause error in the count, though not a very considerable error in 
most cases. (To see Newton's rings we should get our eyes near 
to the level of the counting chamber so that the light from window 
or lamp is reflected from the surface of the cover-glass.) 

^ If we have to pause before going on to the next step, we must take care 
to roll and shake the pipette again when ready to proceed. 

2 In accordance with Meissen's suggestion Zeiss now supplies this apparatus 
with a groove in the glass disc outside the "moat," whereby communication 
is established between the latter and the external air. Thus the results of 
counting are made independent of diiferenccs in atmospheric pressure. 



16 



CLINICAL BLOOD EXAMINATION. 



If the above conditions are not all fulfilled, tlie instrument 
should be washed and another drop tried, after shaking the pipette 
and blowing out a few drops as before. 

The cover-glass must be let down as soon as possible after the 
drop has been put on the disc A, and before the corpuscles have 
time to settle. It is best to let it down with a needle as in mount- 
ing microscopic specimens. 

Counting. 

(d) After waiting two or three minutes so that the corpuscles 
may settle thoroughly upon the space ruled off on the disc A, " the 
whole blood-covered area of the ruled slide should be examined first 



OlOOmin 




C.Zeiss 

Jena 



Fiu. 5.— Tbouiu-Zeiss Counting Slide. A, Ruled dis-c. 

by low power, and, no matter what distribution obtains over the 
ruled square, if over the whole field the cells are not quite uni- 
formly distributed, the slide should be cleaned up and another 
drop examined " (Emerson). 

If the distribution seems everywhere uniform, the counting is 
begun, using preferably an objective 5 of Leitz or D of Zeiss and a 
No. 1 or 2 eyepiece. 

The central part of the ruled space on the surface of Zappert's 
counting chamber (A, Fig. 5) is divided into four hundred squares, 
every group of sixteen squares being enclosed in double lines to 
make it easier to know how many squares we have counted (see Fig. 
6). Including the squares with double lines we have a group con- 
taining thirty-six small squares, a group convenient to count at one 
time as it just about fills the field of the objective Leitz No. 5, or 
Zeiss D with a No. 2 eyepiece. 

To avoid considerable error we should count the corpuscles in 
five fields of thirty-six squares each, such as is shown in Fig. 6, 



COUNTING THE CORPUSCLES. 



17 



taking the fields in various parts of the whole ruled space. The 
instrument should then be washed ' and the whole process rei^eated 
with a second drop. If the count of the second drop differs widely 
from that of the first, a third drop should be counted, and the aver- 
age taken of those two which are most nearly alike. Thus at least 
three hundred and sixty small squares should be counted; with such 
a number the error is not over three per cent for practised observers.' 
In normal blood this means counting about 2,160 corpuscles, as six 
or seven to a small square ^ c 

is about the normal average 
when we are asmg a dilu- 
tion of 1 : 200 such as has 
been described (twelve to 
fourteen cells per square 
in a dilution of 1 : 100 ) . 

Among the difficulties 
encountered in counting is 
the presence of a few cor- 
23uscles on or touching one 
or more of the lines boimd- 
i)u/the space to be counted. 
Shall we count these out 
or in? 

In counting, for in- 
stance, a field like that in 
Fig. 6, what are we to do with the cells which sit astride the lines 
AA, BB, etc.? 

To get round this difficulty, it is best to make it a rule to count 
in all the corpuscles on or touching some two of the boundary lines 
{e.f/., A A and BB) and to take no notice of any cell on or touching 
the lines CC and DD. In this way the exclusions just balance the 
inclusions. Of course all cells luithin these outer boundary lines 
are to be counted whatever their position. 

Beyond this the details must be settled by each man for himself. 
My own habit is to count through the squares in the order indicated 
by the track of the serpentine arrow in the accompanying Fig. 7, 
and to count by twos or threes. 

^ Use only water — alcohol dissolves the cement which holds the ruled disc 
, in place. 

2 See Reinert's "Zahlung der Blutkorperchen," Leipzig, 1891, p. 48 et seq. 

a 



0° 
c 





o 

o 


o 


^o o 
)0 o 


o o 
o o 


o o 
o 


o 


o 


o 


QOO 


o 


°r 


oo o 
Q 


> °o 


o o 


OoO 


o 


o 


o 


O^ 


o 


o 

1 c 


o o 


o o 


o 




o 


.o 


°o- 


oOoo 




o 
o 


o 


o o 
o o 

oo 


oo 


o o 


O < o 


o 




o o 
o o 


O o 


o 
o 
o 


o 
o 


Oo 

o o 
ooo 


) o ° 

o o 


0"o 
o o 


oc 

Oo 

o 
o o 


o 
oo 

o 


o 
o 
o 


o o 
o o 


o o o 
P o 
o 


o 
o 


o 
o 


OOo 
) 00 O 


o 
}00 o 


° o 


o°o 




o 

o 


o 

o 




o 




o 
o 


< 

o 






°0o 
o o 

Oo 


O O 
OOo 

Oo 


o 
o 
o 





o o 


O 


) 


) o 


o 

° 


o^" 


Oo. 


, oo 





oO 


o 










) Oo 


o.^o 


o 


>o 


o° 


o° 


^o- 


° 





o 
o 


°o° 
o o 


O 




°o 
'°o 

O o 


3o 
o , 


1 


o^o 



A C 

Fig. 6.— Field of Thirty-six Squares on Ruled Disc of 
Thoma-Zeiss Counter Covered with Normal Blood 
Diluted Two Hundred Times. 



18 



CLINICAL BLOOD EXAMINATION. 



A movable stage makes the counting easier, especially for be- 
ginners. Either natural or artificial light may be used, with a 
small aperture d.iai)hragm, and if the instruments are clean and the 
diluting solution fresh and free from sediment,' there is no diffi- 
culty in deciding how many cells each square contains, and no ex- 
traneous fragments to be 
excluded. We must dis- 
~ tinguish the white corpus- 
cles from the red, not by 
their size but by their 
stain if Toisson's solu- 
tion is used, otherwise by 

— tlieir peculiar shining 
look when the lens is 

— drawn up so as to put the 
red cells slightly out of 

~ focus. The blood plates 
~ are not noticeable and 
lead to no errors. 

AVhen the number of 

Fig. 7.— The Arrow Indicates the Order in which the corpuscles in 360 squares 
Squares are Counted. , , ^ , 

has been counted the 
number is divided by 360 and multiplied by 800,000 (i.e., by 200 
to make up for dilution and then by 4,000, because each square 
is equivalent to ^oVo" ^^ ^ cubic millimetre), which gives us the 
number of corpuscles per cubic millimetre. 

These figures need not be committed to memory, for we have 
marked on the instruments used all the data necessary for the cal- 
culation, Le.y the dilution figures on the pipette and the area and 
depth of a single square on the counting slide - 

(e) The importance of cleaning the inpette as soon as the count- 
ing is done is so great that it should be reckoned as one of the 
regular steps on every count. First water, then alcohol, and lastly 
ether must be sucked into the pipette and brought into contact with 
every part of the bulb and tube. After this air must be sucked or 
pumped through the tube until it is perfectly dry and the glass ball 
will roll about freely in the bulb without sticking anywhere. 

These precautions take but two or three minutes, and if they are 

•Most diluting solutions precipitate or accumulate spores, and need to be^ 
frequently renewed or filtered. 



COUNTING THE CORPUSCLES. 19 

omitted and the blood dries in the pipette, it may take several 
hours' work to gat it clean. Further, if it is not thoroughly dried 
after cleaning, the mixing of the blood when it is used next cannot 
be done accurately. 

The first three steps of the above process {i,e., the obtaining, 
diluting, and mixing of the blood) must be done as swiftly as is 
compatible with accuracy, but when once the blood is mixed in the 
pipette it can be kept there indefinitely and counted at leisure. 
None of the corpuscles are destroyed or lost, and if the bulb is 
thoroughly rolled and shaken up whenever we are ready to count 
the blood, no error results from keeping it twenty-four hours or 
more in the pipette. 

It is not necessary, therefore, to carry a microscope to the pa- 
tient's house or bedside; the pipette and the diluting solution are 
all that we need to take with us, and when the blood is mixed in 
the pipette, the latter' s ends can be closed with a rubber band, and 
the blood carried home and counted at leisure . The pipette should 
be kept approximately horizontal during the transit. 

CouxTixG thp: White Corpuscles. 

To make a reasonably accurate count of white corpuscles, using 
the "red counter " and the dilution of 1 : 100 or 1 : 200, we need to 
count an immense number of squares, far more than was necessary 
in estimating the red cells — in fact, at least ten times the whole 
ruled space. It is therefore far quicker and more accurate to use 
the " white counter " or large-bore pipette with a diluting solution 
which renders the red cells invisible and leaves only the white to be 
counted. Such a solution is the one-half of one-per-cent solution 
of glacial acetic acid in water. With this the white corpuscles 
stand out very clearly and the red can barely be seen at alL The 
technique is the same as that already described, with the following 
exceptions : 

1. The drop of blood needed is nearly three times as large as 
that used in the " red counter " ; it is about as big as can be made to 
stay on the ear without rolling off, even if we draw blood only to 
the mark 0. 5. If we draw blood to the mark 1, as advised by Turck, 
we must make a deeper puncture and suck in the blood as it fiows 
without waiting for the formation of drops. 

2- The bore of the tube being large, it fills and empties more 



20 CLINICAL BLOOD EXAMINATION. 

readily. Hence our suctiou must be gentler, and it is rather harder 
to stop exactly at the mark 11. For the same reason the diluted 
blood will run out of the pii)ette if the latter is nut kei>t nearly 
horizontal, and the bottle of diluting solution should accordingh' Ije 
tipx^ed up as Ave plunge in the point of the pipette, so that the latter 
is depressed as little and for as short a time as possible before suc- 
tion begins. 

3. Zappert's modification of the Thoina-Zeiss counting chamber 
should be used. Zappert's counting chamber (now supplied Ijy 
Zeiss at the same price as the ordinary one, i.r., 15 marks) differs 
from that ordinarily used in that the central s(piare millimetre is 
surrounded by eight undivided squares of the same size (see Fig. 
10). With this ruling one counts first the number of leucocytes in 
,the central square (about 35 in normal blood) and then in eacli of 
the surrounding undivided squares. This gives us a total of about 
300 leucocytes (in normal blood) as a basis for our calculations. 
The total so obtained is divided by 9, and then multiplied by 200 
(provided we have diluted 1 : 20). 

The advantages of the large-bore pipette are obvious. The only 
drawback is its expanse. The technique is not at all difficult. 

Counting Both lied and WJilfe CcUx ir'dJi fJir Sanif Pipf'ttc 

We may avoid buying both large-bore and small-bore pii)ettes in 
one of the following ways : 

1. We can count both red and white corpuscles with the "red 
counter." 

2. We can count both red and white corpuscles with the " white 
counter." 

The reason why we cannot use the "red counter" for counting 
white cells, unless modified in some way, is that in the whole ruled 
surface of the counting chamber not more than three or four white 
corpuscles are to be found in normal blood when diluted two hun- 
dred times. If we dilute less, we cannot see the cells distinctly, 
because they are so crowded. If we find, say, three white corpus- 
cles as the number to be used as a basis in calculating the number 
of white cells in a cubic millimetre, the chance of error is very 
great, the multiplier being so large (2,000) and the multiplicand so 
small (3). 

To get over this difficulty we may utilize the cells spread over 



COUNTING THE CORPUSCLES. 



21 



the disc of the counting chamber outside the ruled simce in one of 
the following ways : 

(a) Bij measuring the field of the objective used. The writer's 
objective, Iso. 5 of Leitz, has a field of very nearly one-quarter of 
a square millimetre or one-quarter of the 
whole ruled space. Four fields of this 
lens, taken anywhere outside the ruled 
space, therefore, contain the same number 
of cells as will cover the whole four hun- 
dred small ruled squares. 

(I)) Another method is as follows: 
Cut out of black cardboard a square hole 
(see Fig. 8) of such a size that it will fit 
into the tube of the eyepiece — the square 
aperture allowing a space of just one- 
quarter of a millimetre (one hundred of the ruled squares) to be 
seen through it with a given objective (say Leitz No. 5). Four 
fields as seen through such an aperture can then be counted in vari- 
ous parts of the slide outside the ruled space as explained above. 




Fig. 8. 




Fig, 9.— Zappert's Countinpf Chamber. 



(c) For any one living where microscopic ruling on glass can be 
done at a moderate cost, by far the best way is to have the rest of 
the disc A (Fig. 5) ruled off as shown in Fig. 9. Leitz and Zeiss 



22 CLINICAL BLOOD EXAMINATION. 

now supply instruments so ruled. I have not been able to liear of 
any one in America who could, do such work at a moderate expense. 
Whatever method of counting white corpuscles is adopted, we 
ought to have at least one hundred corpuscles actually counted to 
use as the multiplicand of our computation. A single drop from 
the white counter with a dilution of 1 : 10 gives us normally about 
seventy Avhite corpuscles in the four hundred ruled spaces, and 
by repeating the process with a second drop the result may be made 
reasonably accurate. This was the method adopted by Kieder ' in 
the immense nund^er of counts made by him. 

11. J)i(i']i(i Ill's Motlifiril llannorijfomater. 

In the Edinburgh Mi-dinil Journal for October, 1897, Herbert 
E. Durham, of Cambridge, England, describes a self-filling cajiil- 
lary pipette which has considerable advantages over the ordinary 
Thoma-Zeiss instrument. The account of the device is here given 
in liis own words.' 

" As in the Gowers' instrument, there is a separate capillary 
pipette for measuring tlie blood, one for measuring the diluting 
fluid, a mixing vessel, and the counting chamber. A few words 
may be said about each of these. 

" Ccqnllary I*ipette. — There is an obvious advantage in the use 
of a self-measuring pipette. It cannot go wrong by accident. Dur- 

N 



Fig. 10.— Cross-section of Durham's Automatic Blood-Pipette. T, Glass tube (like that of 
medicine-dropper) ; iV, rubbei- nipple (like that of medicine-dropper); ?/, perforation in the 
nipple ; c, cork holder, perforated by capillary pipette. 

ham uses small pieces of thick- walled capillary tube — 5 and 10 
c.mm. in capacity. Such a pipette can readily be cleared by pass- 
ing a })iece of darning cotton by means of a needle through the bore 
of the pipette. It is best to wet the end of the cotton with ether. 

" Any one who has worked much with the Thoma-Zeiss pipette 
will know how troublesome it is to clean, especially when a number 
of observations have to be made in a limited time. The tin 3' pipette 
is mounted by means of a small cork (c) in a large glass tube (T), 

' "Beitrage zur Kenntniss der Leucocytosis," Leipzig, 1892 (Vogel). 





COUNTING THE CORPUSCLES. 23 

which is provided with a rubber nipple (J^), having a lateral per- 
foration (27) (Fig. 10) 

"The mljcing vessel consists of a small test tube (2| x y-g in. 
for 1 c.c, or 2| x f in. for 0.5 c.c). Several such tubes may be 
kept, so that a number of observations can be made if necessary. 
For thoroughly mixing the blood and diluting fluid, one or more small 
glass globules are placed in the tube. By using different colored 
glass globules, different specimens can be readily differentiated. 

"For ineasufing the diluting fluid, ]ilpetfes containing 1 and 0.5 
c.c. are used ; these are remarked at 995 and 990 c.mm. and 495 
and 490 c.mm. respectively. With these graduations the following 
dilutions may be obtained : 1 : 200, 1 : 100, and 1 : 50, with the ap- 
propriate capillary pipette. 

" Having measured the diluting fluid, according to the eventual 
dilation desired, the blood capillary is filled by touching the exud- 
ing drop of blood and allowing it to completely fill itself. 

"The hole in the nipple allows free air-way so that there is no 
hindrance to the action of capillarity. When filled, any blood on 
the outside of the pipette is rapidly wiped off, and the tube is in- 
serted into the mixer until the point is one-half to three-fourths of 
an inch above the level of the contained liquid. 

"The nipple is then held in such a way that the hole lies under 
the thumb of the operator. When this is the case it is slightly 
squeezed, and then, while the pressure is continued, the bulb is 
rotated so that the hole is free again. In this way the blood is 
squirted out, but not sucked back again. In order to wash out the 
remains of the blood the point of the capillary is dropped into the 
diluting fluid; the bore instantly fills itself. It is then withdrawn 
and the pressure and rotation of the nipple are repeated. This has 
to be repeated several times, and occupies a few seconds of time. 

" To mix the blood and diluting fluid thoroughly, the mixer is 
placed between the opposed hands, which are rubbed backward and 
forward; the mixer is rotated thereby, and the glass globules cause 
a thorough dis|)ersion of the corpuscles in the fluid. 

" A drop of sufficient size is then placed upon the counting cham- 
ber, and the cover slip is slipped on sideways in the usual way. I 
prefer the Thoma-Zeiss counting chamber. 

" The advantages of this method are ; 

"1. The ease and thoroughness with which the pipette can be 
cleaned. 



24 CLINICAL BLOOD EXAMINATION. 

"2. The manifest advantage of the self-measnrement of the 

blood. 

"3. The avoidance of the objectionable necessity of using the 
mouth to suck fluids into the pipette. 

"4. The measurement of the diluent can be done carefully 
and calmly beforehand, and any error corrected without taking any 
more blood. 

"5. The greatly smaller cost of the pipette. 

" 6. The same pipette is useful for making various dilutions in 
serum diagnosis, by using several mixing vessels tilled beforehand 
with dilute fluid." 



CHAPTER III. 

OLIVER'S H^MOCYTOMETER— CENTRIFUGALIZING THE BLOOD 
—HEMOGLOBIN ESTIMATION— SPECIFIC GRAVITY- 
STAINED SPECIMENS— THE IODINE REACTION 
—BACTERIOLOGICAL EXAMINATION. 

Oliver's H.emocytometer. 

Recextly a method of estimating corpuscles by means of their 
optical effect, and without directly counting them, has been intro- 
duced by Dr. Oliver. For practical purposes an actual counting of 
the corpuscles must be considered a necessity; not only since the 
number of leucocytes is not without importance {e.g., in the diag- 
nosis of enteric fever), but also since these cells maybe so abundant 
that they may interfere with the use of optical methods, as in the 
case of leukaemia. Nevertheless the instrument is very accurate 
and useful in many cases. Its principle is based on the fact that if 
a small quantity of blood is gradually diluted with Ha^^em's solu- 
tion ^ in a test tube whose sides are flattened so that its mouth forms 
a rectangle about 15 mm. by 5 mm., and a candle flame is looked 
at through the mixture, there is to be seen, when a certain degree 
of dilution is reached, a bright horizontal line on the glass. This 
line is made up of a large number of minute images of the flame, 
produced by the longitudinal striation of the glass. If the quan- 
tity and quality of blood used are in every instance the same, the 
degree of opacity depends wholly on the amount of Hayem's solu- 
tion added. It is found that with normal blood the amount of 
diluting solution necessary to allow the image of the candle flame 
to be seen through the mixture is always the same, and can be verj^ 
accurately fixed, so that a variation of one per cent in the number 
of corpuscles can be distinguished by noting the amount of diluting 

* Hydrargyri percliloridi 0. 5 gm. 

Sodii chloridi 1.0 " 

Sodii sulphatis 5.0 " 

Aquae destillatse 200.0 c.c. 



26 CLINICAL BLOOD EXAMINATION. 

solution whicli must be added before the image of the Hame ap- 
pears. To collect the blood, Oliver uses a capillary pipette cou- 




FiG. 11.— Oliver's Hcemooytometer. A, Graduated mixing tube; P, capillary pipette: 3/, 
dropper, with rubber nozzle fltttinjr tlie capillary pii)ette. 

taining about 10 c.mm. (oue large drop), and used exactly in the 
same way as the v. Fleischl capillary pipette (see Fig. 11). 

One pipette full of normal blood is gradually diluted in the flat- 
tened tube with Hayem's solution until a bright horizontal line 
caused by the image of candle flame becomes visible through the 
mixture. The x^oint to which the column of the mixture then 
reaches is marked 100, and the space between that point and the 
bottom of the tube is divided into 100 equal parts. The point 
marked 100 is then equivalent to 5,000,000 red corpuscles; 90 = 
4,500,000, 80 == 4,000,000, and so on, each degree on the scale 
corresponding to a difference of 50,000 corpuscles (Tig. 11). 

Use of Olivers Hcemoeytometer. 

The capillary pipette is first thoroughlj- cleaned and dried by 
passing through it a needle and thread saturated with water and 
then with alcohol and ether. It is then filled in the usual wa}', 



OLIVER S H^MOCYTOMETER. 



27 



and the outside carefully and quickly wiped if necessary. The 
medicine dropper (previously filled with Hayeni solution) is then 
connected with the polished blunt end of the pipette by means of 
the rubber tube (Fig. 11), and blood washed into the test tube. 
Speed is essential, else coagulation occurs. If the previous haemo- 
globin estimation has shown ninety to one hundred per cent of col- 
oring matter, we can safely add the diluting solution rapidly until 
the point marked 80 is reached. If the coloring matter is lower we 
must cease our rapid dilution correspondingly sooner. When we 
get near the point at which the flame image is likely to appear, the 
diluting fluid must be added a few drops at a time. After each 
addition put the thumb 
over the mouth of the tube 
and turn it upside down 
once or twice to mix the 
blood thoroughly, wiping 
the thumb each time on 
the edge of the tube so as 
to put back what fluid has 
adhered to it. At a cer- 
tain point the image will 
suddenly become visible. 
It is seen soonest if we ro- 
tate the tube on its long 
axis, as the image Ijecomes 
visible earliest at the sides 
01 the tube, but dilution 
should be continued drop 
by drop until the horizon- 
tal line of light is just 
visible across the short 
diameter of the tube. The 
appearance of the incom- 
plete line at the sides is 
a constant forerunner of 
the complete transverse 

line, and should put one on one's guard, as very close watching 
is needed to recognize it without overstepping the necessary dilu- 
tion. The opacity remains uniform for many minutes. The whole 
process should be carried on in a perfectly dark room, and the dif- 




FiG. 12.— Showinpr the Method of Holding Oliver's 
Haemocytometer. 



28 CLINICAL BLOOD EXAMINATION. 

fused light of the candle must be shut off from the eye. This is 
best done by fitting the tube into the hand, as shown in Fig. 12, 
with the long axis in line with the candle, holding the tube close to 
the eye, and standing about ten feet from the candle. In the use 
of both of his instruments Oliver employs only the small wax can- 
dles known as Christmas candles, whose flame is of the most con- 
venient size. 

After some experience witli this instrument I find it simple, eye- 
saving, rapid, and sufficiently accurate in cases not associated with 
marked ansemia, as indicated by the previous haemoglobin test. Its 
drawbacks are the impossibility of making any estimate of the white 
corpuscles with it and its gross inaccuracy in cases of severe anaemia 
(see Emerson, Johns Boiihins Bidl., January, 1903, and Baumgar- 
ten, Johns Hopkins Bull., July, 1902). 

The H.EiVIATOCKIT. 

The haematocrit of Hedin lias undergone considerable modifica- 
tion and improvement and as remodelled and improved by Judson 
Daland has been used to some extent in this country. Its direct 
and obvious object is simply to ascertain the relative volume or 
mass of the corpuscles and of the plasma in a drop of blood; but 
the hope of its advocates has usually been that it would supplant 
entirely or mostly the long, tedious, and eye-destroying process of 
counting with the Thoma-Zeiss instrument. 

To use the Daland hsematocrit Ave prick the ear as usual and 
with the help of a bit of rubber tube attached to one end of the 
capillary tube (Fig. 13) suck in enough blood to fill it entirely. 

As soon as it is full, put the finger (greased with vaseline) 
tightly over the free end of the glass tube and then, hut not till tlum. 
draw off the rubber tube and adjust the glass as quickl}- as possible 
in the place prepared for it on one of the horizontal arms of the 
whirling machine (Fig. 13). A similar tube (empty) should be put 
on the other arm of the crosspiece to make the balance true. The 
handle of the instrument is then revolved at least seventy times a 
minute for two minutes, at the end of which time (sometimes less) 
the column of blood cells is packed so tight that no further whirling 
has any effect on its length. 

To estimate the number of red corpuscles from the length of the 
column, we call each degree of the scale on the tube 100,000 cells. 



CENTRIFUGALIZING THE BLOOD. 



29 



or a little more. Thus if the blood column in the tube ends at 
about the mark 50, we consider that the blood has rather more than 
5,000,000 red corpuscles per cubic millimetre. So far all observers 
agree on the figures, but as to just how much more or less than 
100,000 each degree on the scale is 
worth there is some variation between 
different observers. Daland ' finds that 
the degree of the scale on the capillary 
tube corresponds to 99,390 corpuscles. 

So far as I can learn, the use of this 
instrument in Europe has been chiefly 
for the direct information it affords as 
to the volume of the red cells and the 
amount of respiratory surface in the 
blood, rather than for the indirect in- 
formation it may give us as to the niim- 
her of the red cells. It does not seem 
as yet to be supplanting the Thoma- 
Zeiss counter. 

Its bulk and the noise it makes 
must for the present, I think, prevent 
its extensive use outside of hospitals, fig. la 
The noise it makes is a very loud and 
disagreeable one, and will deter many 
from using it in private practice. 

Emil Aspelin ("Rlineberg's Fest- 
schrift," 1903) has recently made a 
number of experiments with a modified 
instrument, using a longer tube and a 

mixing bulb like that in the Thoma-Zeiss instrument. Here he 
mixes the blood with a diluting solution, and after thorough cen- 
trifugalization is able to estimate with reasonable correctness the 
number of leucocytes as well as of red cells. Still the time con- 
sumed is greater than that necessary to make a count of white cells 
with the Thoma-Zeiss instrument, and for the red cells the new 
instrument, even in Aspelin's hands, is often far from accurate. 

Emerson (Johns Ho^ykins Bull., January, 1903) finds the haema- 
tocrit "useful in determining the presence of lipaemia, cholsemia, 
hsemoglobinsemia, etc., but not to count the cells." 
'University Med. Mag., November, 1891. 




Daland's Haematocrit. Two 
capillary tubes in place oa the hori- 
zontal whirling beam. The instru- 
ment is to be fastened to the edge 
of some solid and bulky piece of 
furniture by means of the tbumb 
screw seen at the bottom of the cut. 
If not very tightly secured, it will 
work loose when the handle is re- 
volved rapidly. 



30 CLINICAL BLOOD EXAMINATION. 



H.EMOGLOBix Estimation. 

1. Tallqvist's Haemoglobinoineter. 

2. Dare's 

3. Oliver's 

4. V. Fleischl's 

Until recently the instrument most used both here and in Europe 
was that of v. Fleischl. In France Hayem rules supreme in the 
matter of instruments, as in everything else concerning the blood, 
and in England .Oliver's apparatus is used to a certain extent. 
Very recently, however, a contrivance originated by Tallqvist ' has 
come into use and deserves, in my judgment, to supplant all others 
in clinical work. I shall therefore describe it hrst. 

I. Tallqvisfs Mfv niogJ ohhi onu'tc r 

A drop of undiluted blood is soaked into a bit of filter paper of 
standard quality and compared (by ordinary reflected daylight) 
with a paper color scale of ten tints, ranging from ten per cent to 
one hundred per cent. The scale was prepared by imitating in 
water color the tint of the blood of anaemic patients (using the v. 
Fleischl instrument) when soaked into the standard filter paper. 
The water-color standard colors were then reproduced in lithograph, 
and the lithographed scale bound up with fifty sheets of the stand- 
ard filter paper makes an apparatus which can be easily slipped 
into the pocket and carried to the bedside. 

In making the comparison the blood stain is put against ■ a back- 
ground of white filter paper beside the color scale, and moved along 
until a match is found. The comparison should be made as soon 
as the stain has lost its humid gloss and before it is thoroughly 
dry. Artificial light cannot be used. Errors of ten per cent are 
possible, but it is my belief that far greater errors than this are 
frequently made with v. Fleischl's or Oliver's instrument in the 
hands of the great majority of physicians. Tallqvist's scale costs 
but $1.25, and can be used by any one with sufficient accuracy for 
practical purposes, and with a celerity that makes haemoglobin esti- 
mation no more of an undertaking than feeling, the pulse. I have 

1 Tallqvist, St. Paul Med. Jour., May, 1900. 

2 Never blot it. 



HAEMOGLOBIN ESTIMATION. 31 

used the instrument in several hundred cases, and liave never yet 
been misled by it, nor found a greater error than ten pev cent in 
comparison with Oliver's 'or Dare's instrument. 

II. Dare^s ^ Htemoglohinometer. 

This excellent instrument is undoubtedly more accurate than 
Tallqvisfs, and would be preferable to all others but for its cost 
(f 20), its bulk, and the time necessary to make an observation and 
to clean the parts. 

As in Tallqvisfs method, undiluted blood is used, and this con- 
stitutes an advantage over both v. Fleischl's and Oliver's instru- 
ments. The blood is drawn by capillary attraction into the slit 
between two slabs of glass, one transparent, the other translucent 
and white, so as to diffuse the light used for illumination. 

The color of the blood is then compared with different portions 
of a circular disc of colored glass revolved by means of a thumb 
screw so that different tints are successively brought side by side 
with the blood tint. Transmitted light from a candle is used for 
illumination, and the observation is made through a tube, which 
effectually excludes all extraneous light. As we turn the screw 
and bring different tints of the glass standard into comparison with 
the layer of undiluted blood, the percentage of haemoglobin can be 
read off from the etched scale which appears at a point opposite the 
color aperture. The sharply bevelled edge of the openin.af rests 
directly over the reading indicated. A pivoted black screen pro- 
tects the observer's eyes from the direct light of the candle, and 
may occasionally be brought over the color apertures so as to rest 
the eye. 

The instrument is so made that blood film and standard color 
disc are viewed side by side in a horizontal plane through two cir- 
cular holes 5 mm. in diameter which are considerably magnified by 
a lens in the telescoping camera tube. 

In using the instrument we need no dark room — a great advan- 
tage. The instrument is simply pointed at some dark surface — a 
dark coat or corner. In order that the blood and the color disc 
should be equally lighted, it is essential to see that any curve that 
exists in the candle wick should point straight toward or away from 
the centre of the instrument in line with the juncture of the springs 
which support the candle. 

iPhila. Med. Jour., October, 1900. 



32 CLINICAL BLOOD EXAMINATION. 

The reading should be completed before the blood fihu begins to 
shrink in from the edges, i.e., within ten minutes. 
The advantages of Dare's instrument are : 

1. Its accuracy; using undiluted blood and making allowance as 
it does for the color curve, it is, I believe, more accurate than any 
other clinically available instrument. 

2. Leucocytosis does not disturb the reading (as it does in v; 
Fleischl's instrument). 

3. The errors and waste of time incident upon dilution are 
avoided, since the instrument uses undiluted blood. 

4. No dark room is needed. 

5. It can be used and cleansed much more quickly than any 
other instrument except Tallqvist's. 

My reason for preferring Tallqvist's instrument despite thes(^ 
merits of Dare's are: 

1. Because accuracy greater than that obtainable with Tallqvist's 
instrument is seldom practically important. 

2. Because an observation can be made with Tallqvist's haemo- 
globinometer in about one one-tenth of the time needed for using 
any other instrument, i.r., in about twenty-five seconds. 

3. Because the Tallqvist instrument takes so little room and 
needs no cleaning or preparing for use. 

4. Because it is so cheap. 

Ill Olircr's Hannoglohinometer. 

Oliver's instrument corrects two errors whicli are inherent in v. 
Fleischl's. 

1. It has no sliding scale of color, but compares the blood tint 
successively with definite tints of glass, each of which is even. 
The tints are worked out to correspond to the specific dilution curve 
of blood, for: 

2. Since every colored liquid changes color at a different rate 
when diluted, the dilution curve of blood does not correspond to that 
of glass (which, behaves in this respect like a liquid). The glass 
wedge of v. Fleischl's instrument represents a single color regularly 
diluted and does not correspond in its degrees to the colors of blood 
diluted at a similar rate. The scale of Dr. Oliver's instrument is 
measured to correspond to the actual colors of the blood's dilution 
curve by means of the tintometer. 

In other respects the principle of the instrument is like v. 



HEMOGLOBIN ESTIMATION. 



33 



Fleisehl's, and the method of using the two is practically the same 
except that in Oliver's reflected light is used instead of transmitted 
light. Oliver's instrument consists of a series of twelve tinted glass 
discs corresponding to the haemoglobin percentages from 10 to 120 




FIG. 14. 



-Oliver's Hgeinoglobinometer. r/. Standard color discs ; h, capillary pipette ; c, washing 
tube ; cl, mixing cell. 



and arranged in two rows (see Fig, 14, c/). The intermediate de- 
grees are measured by means of " riders " of colored glass, which 
can be laid on top of the primary color discs so as to deepen the 
tint seen 

The capillary pipette (Fig. 14, l>) is somewhat stouter than v. 
Fleischl's, but is used in the same way to collect the blood, which 
is then forced out of it with water from a medicine dropper (which 
is fitted with a rubber tube to slip over the blunt end of the j)ipette) 
(Fig. 14, c) and washed into a mixing cell (Fig. 14, d) similar to 
V. Fleischl's, except for the absence of a central partition. Here 
the blood is mixed in the usual way with water and the cell filled 
to the brim and covered with a small glass plate; a bubble always 
forms, but by turning the cell or moving the cover-glass we can 
usually get the troublesome shadow thrown by the bubble out of 
the color field. The blood thus prepared is brought close to the 
3 



34 CLINICAL BLOOD EXAMINATION. 

scale and there compared with the tint of the different standard 
color discs. If it matches one of them the observation is complete ; 
if not we use one of the glass riders, wliich enables us to read within 
two and a half degrees. A fuller set of riders can be obtained so 
as to make it possible to read down to one per cent. 

The standard is usually arranged for candle light, but another 
set of discs can be obtained adjusted to daylight readings. The 
latter are less accurate. The same precautions as to the exclusion 
of outer light by means of a " hydroscope " tube, resting the eye 
frequently, etc., must be observed with this instrument as with v. 
Fleischl's. [It can be obtained of J. H. Smith & Cie., Zurich 
(Wollishoften), for 115 francs plus duties and expressage, or of the 
Tintometer Company, 6 Farringdon Avenue, London, E. C] The 
candle should be placed three or four inclu\s from the instrument 
and arranged to light both the blood and tlu; ccjlor discs alike. 

A word as to the use of the riders. The instrument as used for 
clinical work usually has two riders : the one having the deeper 
tint is used on the upper half of the scale, the ether on the lower. 
Suppose we have decided that the blood color is between 60 and 70. 
Put the rider on the 60 disc and compare again. If the blood is 
darker than the 60 disc plus the rider, the percentage is approxi- 
mately 671 (since it is higher than 60 -f 5 [the rider] and lower than 
70. If it just matches the 60 plus its rider, the reading is 65. If 
the blood is paler than this, yet darker than 60, it is about 62 i. 
An error of about two degrees is obviously inevitable. 

IV. Use of V. FlelscliVs Haimometer. 

(a) Fill on one side of the metallic cell (a, Fig. 16) about one- 
quarter full of distilled water. Put the end of the little pipette 
(B) horizontally into the side of the blood drop, which will at once 
fill the tube by capillary attraction. Quickly wipe away any blood 
that may be on the outside of the pipette. Then put it into the 
water contained in one of the partitions of the metallic cell and 
rattle it quickly back and forth, so that the water may be forced 
in first at one end and then at the other. 

(h) After this the expulsion of the blood may be. completed by 
forcing water from a medicine dropper through the capillary 
pipette and into the compartment where the mixing has been begun. 
Using the metal handle of the pipette, mix the blood and water in 
every part of the compartment. Then fill both compartments of 



HAEMOGLOBIN ESTIMATION 



35 



tlie cell to the brim witli distilled water, and adjust the compart- 
ment containing the clear water so that it comes over the slip of 
colored glass, Avhile through the compartment containing the blood 
light thrown upward by the reflector below passes directly to the 





Fifi 



15. — A, Colored 
jB, capillary 
pipette. 



Fig. 16.— v. Fleischl's Haemometer. a. Partition into wliicli blood 
is put; a\ partition into which water is put; G, mixing cell; 
K, K, colored glass slip (see Fig. 15, A); P, P, metal frame on 
which scale is marked ; R, S, reflector ; T, screw which moves 
the frame, P, P. 



eye« Turn the thumb screw (see Fig. 16, T) back and forth until 
the color of the glass is the same as that of the blood, and read off 
the number on the scale which corresponds to that color. This 
gives the percentage of haemoglobin, 100 being the color of normal 
blood for men and 80-90 for women. 

(c) Matching the colors may be somewhat aided by observing 
the following precautions : 

1. Do not stand (oj' sit') fa cing the light, hut sidfirags. 

2. Use as little light as possible. 

3. Iioll iq) a piece of paper (^p/referahly Mark) into a tube of 
such size that it will fit over the metallic cell (D, Fig. 17), and rest 
on the platform of the instrument. 

4. Use first one eye and then the other, and never look more thaiv 
a few seconds at a. time. 

5. Move the thumh screir vitJt short, quick turns rather thaw 



S6 



CLINICAL BLOOD EXAMINATION. 




B 



slowly and yraduallij, for sudden color changes affect the retina 
more than gradual ones. 

0. If the preliminary reading shows one of thirty per cent or 
less, two or three pipettes full of blood should be used and the 

reading divided I)}- 2 or 8. 

A considerable error can thus 

be avoided. 

Necf^ssary Error a. 
A considerable error is 
absolutely necessary, inas- 
much as the bit of colored 
glass to be seen at any one 
time through the aperture of 
the instrument is not (like 
the blood) all of one tint, but 
includes a vfirlatlon of twenfy 
l^er cent in color, i.e., if the 
glass appearing at one end of 
the aperture is opposite 50 on 
the scale, tluit seen at the 
other end of the aperture aviU 
either be at 30 or at 70. 
To avoid these and other difficulties with v. Fleischl's instru- 
ment various modifications of it have been proposed, the best of 
which is Miescher"s. 

In using Miescher's modification of v. Fleischl's instrument the 
dilution is carried on in a capillar}^ pipette like that of the Thoma- 
Zeiss instrument, distilled water being the diluent. From the mix- 
ing bulb of the pipette the diluted blood is blown into one com- 
partment of each of the two cells (one 15 mm. deep, the other 
12 mm. deep) which are supplied wdth the instrument. The other 
compartment in each cell is filled with water. The grooved cover- 
glass is slid along the projecting partition of each cell, and each 
cell then covered wdth a diaphragm which transmits a ray of light 
corresponding to not more than three degrees of the scale, '' thus 
giving practically a single color of the glass wedge for comparison 
w^ith the blood" (Emerson). Candle light is used. 

The reading of the smaller cell should be four-fifths that of the 
larger, and one reading mav be used to control the other. The 



Fig. n.—L, Ligbt ; ,1 anrl B. liirht positions for 
observer; C, wronsr iiosition for observer; D, 
cell in place. 



SPECIFIC GRAVITY. OV 

table supplied with the instrument translates the data obtained into 
hsemoglobin percentages or grammes per 100 c.c. of blood. 

The instrument is very accurate; but no better than Dare's, 
which costs less than half as much. 

As recently pointed out by Emerson (Joe. cit.), the readings of 
most haemoglobin scales (100 per cent being made to correspond to 
about 13.8 gm. of haemoglobin per 100 c.c. of blood) cannot be 
applied directly to child ren's blood. 

The child under five years has normally but 10 to 16 gm. per 100 
c.c, which would correspond not to 100 per cent, but to 75 to 80 
per cent. Similarly the normal for a child from five to fifteen 
years is 80 per cent; from fifteen to twenty-five years, 88 per cent. 
It would be better, as Emerson says, to express our readings in 
grammes per 100 c.c. rather than in per cent. 

ESTIMATIX(i THE SrE<IFI<; (tKAVITY OF THE BloOD. 

The simplest and most available method for clinical use is that 
of Hammerschlag,^ a modification of Eoy's- method. Chloroform 
is heavier than blood; benzol is lighter. Mix in a urinometer glass 
such quantities of the two that the specific gravity taken by an ordi- 
nary urinometer is about 1059, i.e., that of normal blood. Punc- 
ture the ear, draw a drop of blood into the tube of a Thoma-Zeiss 
pipette, a small medicine dropper, or any other capillary tube, and 
blow it out again into the chloroform-benzol mixture. The blood 
does not mix at all with these liquids, but floats like a red bead. 
If it sinks to the bottom add chloroform, if it rises to the top add 
benzol, mitil finally the drop remains stationary in the body of the 
liquid, showing that its specific gravity is just that of the surround- 
ing mixture. Then take the specific gravity of the liquid, as we 
do of urine, and you have the specific gravity of the drop that 
floated in it. The following precautions are needed : 

1. Have the inside of the urinometer glass perfectly dry and 
clean; otherwise the drop of blood may cling to it and flatten out 
against it. 

2. It is usually well to have more than one drop of blond in 
the glass in case any mishap occurs with the first one.. 

3. Add the chloroform and benzol a few drops at a time, and 

1 Wien. kliu. Wochenschrift. iii.. 1018. 1890. 
- Proceedings of Phv>iolo2:ical Societv, 1884. 



88 CLINICAL BLOOD EXAMINATION. 

after each luUlition stir the whole inixture tliorou^^hly with a glass 
rod , 

4. If we liave reason to suppose the blood will be lighter than 
normal {i.(^., if the hseinoglobin is probably low, vide supra), it 
saves time to start with a lighter mixture of chloroform and benzol. 

5. Avoid having any air within the blood drop. This can gen- 
erally be seen either in the capillary tube or after the drop is in the 
mixture. It is safer to take the wiOJh- jmrfion of the Vdood drawn 
into the capillary tube, as both the first antl the last portions of the 
column are more apt to have air in them. 

6. The whole process should be done as ([uickly as possible, else 
the chloroform or benzol may evaporate or work into the blood <lr()p 
and so affect its weight. 

It is better to have a urinometer with a scale running as high as 
1070, but this is not essential, for the clinically important specific 
gravities are low, not high. 

The importance of the specific gravity of the blood, as hinted 
above, is not so much for itself, but because it runs })arallel to the 
percentage of hsemoglolnn and gives a figure from Avhich the latter 
can be computed. 

The specific gravit\- of the blood varies very little (except in 
dropsy from any cause), and in the corpuscles themselves the vari- 
able element is the haemoglobin.' Conse([uently in most non-drop- 
sical patients the specific gravity of tlie whole blood varies directly 
as the haemoglobin. Tlie following exceptions to this rule must be 
borne in mind. 

1. In leukaemia the specific gravity is relatively higher than the 
haemoglobin on account of the weight of the leucocytes. 

2. In pernicious anaemia with high color index (see below) the 
haemoglobin is about two per cent higher tlian we should gauge it to 
be judging by the specific gravity. 

To estimate the percentage of lu«moglobin from the specific 
gravity, one of the following tables may be used, modified from 
Schmaltz, '' Pathologie des Blutes,-' etc., Leipsic, 1896, using a 
direct weighing method. Apparently a degree of specific gravity 
means much more at the top of the scale {i.e., Q>.^ per cent) than 
at the bottom (1| per cent). This table has been verified by the 
research of Yarrow {University Med. Mar/.. 1899) through compar- 

' Except in dropsy in which the corpuscles themselves may get water- 
soaked. 



SPECIFIC GRAVITY. 



39 



ison with a standard solution of 13.77 gm. of prepared haemoglobin 
in normal salt solution (up to 100 gm.). It appears to be very 
accurate. 



Spec. Gray. 


Haemoglobin. 




Spec. Gray. 


Haemoglobin. 


1030 = 


20 


per 


cent. 


± 


1049 = 


60 per 


cent. ± 


1035 = 


30 




(( 


u 


1051 = 


65 


a a 


1038 = 


35 




u 


(( 


1052 = 


70 


a a 


1041 = 


40 




" 


a 


1053.5 = 


75 


u u 


1042.5 = 


45 




u 


a 


1056 = 


80 


" " 


1045.5 = 


50 




a 


t( 


1057.5 = 


90 


" 


1048 = 


55 




"■ 


(( 


1059 = 


100 


a u 



Studies of Fixer Structures of the Blood, 

The study of dried and stained specimens with the help of the 
aniline dyes gives us much of interest and importance in regard to 
the blood. More can be told about a given case by the study of a 
dried and stained cover-glass specimen than by any other single 
method. . 

Preparation of Cover- Glass Specimens. 

(a) Covers carefully cleaned and polished are arranged at the 
bedside in such position that we can quickly pick them up without 
touching their surfaces (see Fig. 1).' The ear is punctured in the 
usual way, and one of the cover-glasses touched to the summit of 
the drop as soon as it emerges. This cover-glass is then let fall 
upon another in such a way that their corners do not coincide (Fig. 
18). If the covers are clean, the drop spreads at once over their 
whole surface; as soon as it stops spreading, slide off the top one 
without lifting them apart, but exactly in the plane of their sur- 
faces. Have a gas or alcohol flame at hand and dry instantly if 
you want to get the \^v\ best specimens; but this is not at all neces- 
sary for most clinical purposes. The under cover-glass is always 
better spread than the upper. 

The above method needs a good deal of practice, (h) An easier 
way of preparing blood films is as follows : 

Put a moderate sized drop of blood on a glass slide (not a cover- 
glass) near one end. Hold another slide (or a cover-glass) against 

^ I often poise tliem on corks so tliat their corners are readily accessible to 
the fingers. The process of making blood films is far easier if another person 
prepares the drop for us so that we can stand ready with a cover-glass in each 
hand to catch the drop as soon as it emerges. 



40 



CLINICAL BLOOD EXAMINATION, 



the first ill the position shown in Fig. 19. ]\[ove the slide along in 
the direction shown by the arrow so as to spread the blood droj) 
over the whole length of the glass as thinly as possible. The 





/e'OCfjf/<i'Sf^ 



Ik;, is. Fi<;. 19.— Spreading Blood on a Glass Slide. 

quicker the whole process is performed the better will Ije the results. 
After drying the film in the air it can be fixed and stained as below 
described. 

F'lXviKj the Films. 

These films have now to hafxed, and this process is best com- 
bined with that of staining as is done by Wright's method (see 
below). If other staining methods are to be used, the films must 
first be fixed either by heat or by half an hour's immersion in abso- 
lute alcohol and ether (equal parts), or by the same mixture (30 
c.c each) plus five drops of a saturated alcoholic solution of corro- 
sive sublimate (five minutes' immersion), by chromic acid two per 
cent, or by exposure to the vapor of forty-five-per-cent formalde- 
hyde. I have used all these methods, but found none of them to 
compare favorably with Wright's method. 

The method of fixation by alcohol and ether needs little com- 
ment, the cover glasses being simply left in the mixture half an 
hour or as much longer as is convenient. Half an hour is enough. 
For Ehrlich triacid stain we use dry heat. The best way to do this 
is in a dry-heat sterilizer at a temperature of 115°-lo5° C, accord- 
ing to the size and construction of the oven and the kind of stain 
used. The temperature must be watched very closely, and as soon 
as it reaches the desired point the heat should be removed. It 
needs about five minutes to get the temperature to loO° C, and as 
soon as it gets there the specimens should be taken out. The ther- 
mometer bulb must rest as near as possible to the blood films with- 
out actually touching them. 



( 



STAINING. 41 



Staixixg. 



/. W^righf's Method. 

Within the past year hsematological technique has been notably 
simplified and improved by the introduction of a stain far superior 
in my opinion to any previously in use. I refer to Wright's modi- 
fication of Leishman^s stain, which in turn is a modification of Jen- 
ner's. Jeuner introduced the use of methylic alcohol at once as a 
solvent for staining materials and as a means of fixing blood films 
upon glass. Leishman simplified and improved the method of 
using a stain which in itself differs but little from Jenner's. 
Wright showed us a much quicker and easier method of preparing 
the stain, the essential pigments in which are polychrome methylene- 
blue and Grlibler's yellow eosin. Eor details of preparing the 
stain see Wright's article.^ The stain must be kept in a tightly- 
corked bottle since evaporation soon makes it precipitate, and so 
spoils any preparation stained with it. I have noted no deterio- 
ration in bottles used during the last six months. 

The process of staining is quicker and simpler than any other 
known to me, and even if it is not carried out precisely according to 
the directions given below, a fairly presentable specimen is almost 
always to be obtained. 

Techxique. 

1. Drop upon the blood film with a medicine dropper as much 
of the stain as it will hold without spilling off, and leave it there 
for one minute. This is chiefly to fix the film. 

2. Add to the fluid on the cover-glass (or slide) sufficient water 
drop by drop to make visible a greenish metallic scum upon the 
surface. For a ^-inch square cover-glass six to eight drops are 
usually needed, but the exact amount does not make any essential 
difference. Let the stain thus diluted remain for about two min- 
utes upon the film. 

3. Wash the film in tap water and let it stand in water for one 
or two minutes more, or until the thinner portions of the film are 
yellowish pink. Water washes out part of the blue dye and differ- 
entiates the stain. 

.James H. Wright: .Jour. ]\[ed. Research, Januaiy, 1902. 



42 CLINICAL BLOOD EXAMINATION. 

4. Dry cautiously with Ijlottiug paper or filter paper aud mount 
in balsam. 

The whole process should not consume more than five minutes- 
time. (The stain may be had at the Harvard Cooperative Society 
store, Boylston Street, Boston.) 

This stain is the best known to me not only for leucocytes and 
erythrocytes, normal and abnormal, but also for malarial parasites, 
basophilic granulations of red cells, and all purposes for which one 
uses a blood stain at all 

II. JShrlich's Method. 

Far inferior in most respects is Ehrlich's tricolor mixture, which 
is made as follows : 

Saturated watery solution of orange G 6 c.c. 

" " " " acid fuchsiu 4 '* 

To these add a few drops at a time, shaking between each addition 

Saturated watery solution of methyl green 6.6 c.c. 

Then add : 

Glycerin 5 c. c. 

Absolute alcohol 10 " 

Water lo - 

Shake well for one to two minutes. Let stand tw^enty-four hours. 
Do not filter. G. Grtibler's colors are best. 

The staining process is simple. A drop of the stain is simply 
spread over the surface of the cover-glass specimen with a glass rod 
and washed off again with water after five minutes, or as much 
longer as is convenient. If the specimen look too dark (brown or 
red instead of orange-yellow), it is not because of overstaining, but 
because of underheating . 

If overheated, the specimen looks pale lemon yellow to the naked 
eye, and under the microscope everything is blurred and dim. 

The Iodine Reaction. 

lodophilia, so called, is the reaction which the neutrophilic leu- 
cocytes show when brought in contact with a drop of the following 
solution : 

Iodine 1 gm. 

Potassium iodide 3 " 

Water 100 c.c. 

Gum arabic 50 ?m. 



TECHNIQUE. 43 

A drop of this mixture is put ou a slide and into it we press a 
film of blood without any previous fixation or preparation of any- 
kind. Use an excess of the iodine mixture and then squeeze out 
the excess by gentle pressure on the cover-glass lest the dense color 
of the fluid obscure the field. When such a slide of normal blood 
is examined, the red cells are found to be uniformly colored a bright 
yellow upon a much fainter background, while the white corpuscles 
are stained of about the same tint, their nuclei being somewhat 
more refractile. This contrast between the nucleus and protoplasm 
is sufficiently distinct to permit one readily to differentiate the 
various forms of white cells. In certain pathological conditions, 
such as septicaemia or uraemia, the uniform yellow coloration is broken 
by the appearance in the protoplasm of the polymorphonuclear 
neutrophiles of reddish-brown granules, or a diffuse brownish color- 
ation, and by the presence of small and large masses outside the 
corpuscles similarly colored. This condition is the " iodine reac- 
tion," and as suggested is of two distinct types, namely, (1) the 
extracellula]-, and (2) the intracellular. 

1. ExtrnreUnlar Reaction. — The masses seen outside the cells 
are round, oval, or slightly inegular, varying in size from 2 to 6, 
or even 8 // in diameter, and of a copper-red color. They may be 
free, but are usually found in fragments of protoplasm which appear 
to be the debris of broken-down leucocytes. 

2. Intracellular Bearthm (see Figs. 20 and 21).— Within the 
cells the reaction occurs almost invariably in the neutrophiles. 
Here the appearance is extremely varied, the granules being of 
almost any depth of color from a light orange to the deepest 
brown, and of various sizes. They may be scattered evenly through- 
out the protoplasm, grouped about the neucleus, or, in rare cases, 
at the periphery of the cell. In sharp contrast to the round or 
oval extracellular bodies, those w^ithin the cells are for the most 
part irregular in sliape. In many of the neutrophiles the reaction 
is shown not by a granular appearance of the protoplasm, but b}- a 
diffuse brownish discoloration, the depth of which varies within 
wide limits. In rare cases basophiles and myelocytes react, but here 
the picture is a different one, for instead of numy granules scattered 
throughout the protoplasm one finds a more or less distinct single 
row of relatively large brownish areas about the nucleus We have 
never observed any brown color, either diffuse or granular, in the 
eosinophiles. 



44 



CLINICAL BLOOD EXAMINATION. 



It is important to note that in some specimens only a few neu- 
tropliiles are found which are abnormal. Tlie intensity of the color 
appears to be of as much importance as the number of corpuscles 
showing it. Not infrequently a large numl)er of leucocytes are 
seen absolutely unaffected by the iodine soUition l)efore any are 





Fig. 30.— a, strong lodophilia in a Polynu- 
clear Leucocyte ; h. Normoblast. 



Fig. 21.--Moderate lodophilic Reaction in 
Two Polynuclear Leucocytes. 



found with the characteristic coloration. With other cases scarcely 
any normal ones can be demonstrated. In our examinations we 
have, as a routine, counted at least one hundred cells; if in that 
number none are observed with either a diffuse or granular stain, 
we consider the reaction negative. 

Differential Count Iikj. 

The only procedure in the microscopic examination of stained 
specimens which needs any description is that of making the so- 
called " differential count " of the leucocytes (/.^., determining what 
percentage of the leucocytes present belongs to each of the sub- 
varieties as described on pages 60-67). To do this accurately we 
should examine at least five hundred leucocytes — the examination 
being simply the classification of them under their different sub- 
varieties. A movable stage is very convenient though not essen- 
tial for this purpose. With such a stage the technique is simply to 
start with the lens in, say, the upper left-hand corner of the blood 
film and, by turning the screw of the mechanical stage, move the 
preparation slowly past the eye until the upper right-hand corner 
is reached. During this process, as the cells appear in the field they 
are checked off and put down under one or another heading. Then 
move the stage so that the lens is just one field's diameter nearer 
the right-hand lower corner of the preparation, and go back again 
from right to left, following the serpentine track indicated above in 
Fig. 7. To move the lens just one field's diameter we have only to 



BACTERIOL0GICAL EXAMINATION. 45 

fix the eye on a cell at the extreme edge of the field, and then move 
the stage till that cell disappears out of sight on the opposite side of 
the field. Thus we avoid any chance of counting the same cells 
twice, and yet are sure not to miss seeing any. 

As Ave go back and forth in this way, we notice chiefly the 
white cells, of course, but yet keep our eyes open for any unusual 
appearances in the red cells. Usually these move by in a monoto- 
nous stream, one looking much like another, but in pathological 
blood we must always be on the lookout for nucleated red cells, 
degenerative changes, and variations in size and shape. In malarial 
cases, of course, our scrutiny is directed chiefly upon red cells. 

If Ave have not the help of a movable stage Ave try to do the 
same thing moving the slide Avith the fingers. With moderate care 
there is no danger of counting the same cells twice, but we cannot 
help missing a good many altogether, so that although accurate the 
process takes longer. 

When leucocytosis is present, at least one thousand leucocytes 
can be found in a single Avell-spread seven- eighth- inch cover-glass 
specimen. In normal blood Ave may need to go through two or 
three covers. 

Bacteriological Examinatiois^. 

Blood obtained by the ordinary method of puncture is not fit for 
bacteriological examination.' The following is the better way: 

Sterilize the skin over the flexor surface of the bend of the 
elboAv, and Avash off thoroughly the agents used for sterilization 
with boiled Avater or boiled normal salt solution. Have an assist- 
ant grasp the upper arm so as to prevent the venous return and 
distend the large A^eins at the elboAV. Into the most prominent of 
these plunge a sterilized hollow needle connected with the bulb of 
a sterilized syringe. All traces of antiseptics must be carefully 
washed out of the needle and the syringe bulb before using. 

When the needle penetrates the wall of the vein the blood usu- 
ally begins to flow into the bulb of the syringe, and this is hastened 
by gently AvitlulraAving the piston until 5 to 10 c.c. of blood are in 
the bulb. Then AvithdraAV the needle, press a pad of sterilized 
gauze OA^er the wound, and expel the blood before it coagulates 
into a flask of nutrient bouillon or melted agar-agar. 

^ See Ktihnau's comparative experiments in Deut. med. Woch., 1897, 
No. 25. 



46 CLINICAT. BLOOD EXAMINATION. 

The further examination of cultures falls outside the scope of 
this book. 

In the above procedure the only difficulties are : J Sometimes it 
is hard to find a vein and to get the needle into it. 2. Occasional!}' 
we get the needle entirely through the vessel into the tissues on the 
other side. 

If the blood does not flow readily into the bulb one of these two 
mistakes is usuall}^ the cause, but occasionally in those whose ves- 
sels are very small or whose circulation is very feeble (as in the 
moribund) it is very hard to get the requisite amount of blood. 
Only practice helps us to avoid these difficulties. 

The procedure causes hardly more pain than the use of an ordi- 
nary subcutaneous injection; the process of sterilization is usually 
more irksome to the patient than the puncture 

Bleeding is trifling, and within twenty-four hours there is usu- 
ally no trace of the puncture left. A sterilized dressing with mod- 
erate pressure should be applied 

Estimation of the Time and of the Completeness of Coagulation. 

In certain conditions, particularly in acute exanthemata, clot- 
ting is slow or fails to occur. This is still more marked in the 
various forms of the hemorrhagic diathesis. In obstruction in the 
biliary tract, with or without jaundice, clotting may be greatly de- 
layed, and this fact is of great importance to the surgeon with refer- 
ence to the question of operation. 

Hayem has called attention to the fact that in purpura haenior- 
rhagica the blood clot may form, but fail completely to retract. 
He further believes that the blood of pernicious anaemia may be 
distinguished from specimens obtained in cases of secondary anaemia 
by the fact that in pernicious anaemia there is an incomplete forma- 
tion of serum. 

In both these conditions the blood plates are greatly diminished. 
Hayem has found similar changes in some other cachectic con- 
ditions. 

The importance of these facts in the prognosis of purpura may 
be considerable — the severer forms being thus distinguishable from 
the milder types (according to Hayem) even during the remissions 
or non- hemorrhagic stages of the disease. 

For the estimation of coagulation time the simple little instru- 
ment devised by Wright is sufficient. This consists simply of a set 



OTHER METHODS. 47 

of from six to • twelve capillary tubes of about the same calibre 
(0.01 to 0.0125 inch) into each of which a blood column about two 
inches long is aspirated. The tubes are then set perpendicularly 
in a rack and at regular intervals the condition of the blood is tested 
by blowing into one of the tubes. \Yhen coagulation occurs, the 
tubes are found to be blocked with clot. 

Normally coagulation occurs in these tubes in about three min- 
utes. In disease, especially in cases with biliary obstruction, coagu- 
lation may not occur until ten to fifteen minutes have elapsed. 

Other Methods of Blood Examixatiox 

It is perhaps worth while briefly to mention some other methods 
of blood examination of which no account will be. given. 

1. Determination of the alkarinlty of the blood. No accurate 
and clinically available method has yet been devised. Despite the 
interesting work of Kraus, Caro, Lowy, Biernacki, v. Limbeck, and 
others, I am still unable to get hold of any clinically valuable in- 
formation given by the determination of alkalinity. 

2. Resistance of the red coi^niscles to the influence of distilled 
water. As is well known, water breaks up red cells ; but if we add 
a certain amount of alkali, say NaCl, the cells remain uninjured. 
The amount of NaCl which has to be added to prevent the destruc- 
tion of red cells is from 0.44 to 0.48 per cent. Under certain 
pathological conditions it needs either more or less of the salt to 
keep the cells intact, i.e., they possess an increased or diminished 
power of resistance against the destroying influences of distilled 
water. The degree of concentration necessary to maintain red cor- 
puscles intact is known as the isotonic coefficient of the blood as 
stated in terms of a given salt ; 0.44-0.48 is thus the coefficient of 
normal blood corpuscles in NaCl, provided we do not take account 
of any changes in the red cells other than the giving up of their 
haemoglobin. In solutions weaker than 0.44 to 0.48 per cent NaCl 
the haemoglobin leaves the corpuscles; but minor changes — especially 
swelling of the whole cell — may occur in any solution of NaCl 
weaker than 0.9 per cent, so that if we desire for therapeutic pur- 
poses a solution as neutral as possible in relation to the red cells a 
0.9-per-cent NaCl solution is better than a weaker one. 

The resistance of the blood cells to the influence of electricity, 
heat, and mechanical pressure has also been investigated in various 



48 CLINICAL BLOOD EXAMINATION. 

conditions of health and disease. Welch has suggested a possible 
clinical application of these facts. There is much, he says, for the 
view that the number of blood plates is an index of lowered resist- 
ance in the red cells. When resistance is lowered and blood plates 
increase, intravascular thrombosis — so much dreaded in chlorosis, 
so eagerly desired in aneurisms — is more apt to occur. 

3. The amount of solids in a given quantity of blood can be de- 
termined by weighing a given amount of blood before and after six 
hours' drying at 65^ C. Inasmuch as the haemoglobin percentage 
and the specific gravity run practically parallel with the amount 
of solids this method has no considerable clinical value. 

4. The viscositi/ of a S])ecimen of blood may be estimated by 
determining the force necessary to draw it tlirough a glass tube of a 
given length and diameter compared to the force needed to draw an 
equal volume of water through the same tube. Hirsch and Beck 
{Deut. Archiv f. kl'in. Med., April 12th, 1901) have worked out an 
apparatus on this principle and found that judged b}^ this test 
normal blood is 5.1 times as viscid as water, both being tested at 
38° C. Different specimens of normal blood vary from 4.0 to 5.9 
(water = 1) 



PART II. 

PHYSIOLOGY OF THE BLOOD. 



CHAPTER IV 



Only such portions of our knowledge of blood physiology will 
be entered upon here as are necessary for an understanding of the 
small group of pathological changes which can be profitably inves- 
tigated by clinicians. This limits us for the present to the mor- 
phology of the blood, its coloring matter, and its density under 
physiological conditions. 

Appeakaxce of Fkesh ^N'ormal Blood. 

1. lied Corpuscles. 

{a) If the blood is spread thickly the blood discs are often 
arranged in the/br//?, of rouleaux (Fig. 22), which represents a form 
of agglutination. Adding horses' serum to human blood greatly 
increases the tendency to rouleaux formation, while in NaCl solution 
the rouleaux are not formed at all (Shattock : Journ. of Path, cmd 
Bact., 1900, p. 313). The entire absence of this tendency to 
rouleaux formation is x3athological. It is to be avoided, of course, 
as far as possible, as it gives us only the thin edges of the corpuscles 
to look at, and covers up much that we need to study. Thin spread- 
ing of the blood is therefore important. 

(h) There is not much variation from the accurcitely round shape 
of each corpuscle in normal blood, except where one is indented by 
another. As they are moved about by the currents set in motion 
by the gradual drying up of the plasma, and strike against each 
other, they bend, double up, or indent each other like bags of jelly, 
but yet always have a strong tendency' to return elastically to their 
round outline when free from pressure. Thus a corpuscle passing 
through a narrow passage between two leucocytes will be flattened 
out like a worm; but as soon as it emerges on the other side, it will 
be as round as before. 
4 



50 CLINICAL BLOOD EXAMINATION. 

(c) The central hiconcavity of the r-ell, being thinner than the 
rim, is lighter colored. Just how much lighter should be learned 
by practice so that we may detect any abnormal pallor of the corpus- 
des due to lack of haemoglobin. Pallor is to be seen mostly in the 
centre of the cell, which in extreme cases seems almost transparent. 
This is not to be confounded with the highly refractile, glistening- 
white centres seen as a mark of necrosis as soon as the blood begins 
to dry up. A fuller description of these appearances is given in 
the chapter on the malarial organisms, Avith some forms of wliicli 
they may be confounded. 

(d) Slight variations in size are present among normal red discs, 
and here again only practice can teach us where the normal limits 
end and the pathological begin. Cells inay be (pathologically) all 
undersized or all oversized, so that a standard of comparison is not 
always to be looked for in the preparation itself. 

(e) If we focus carefully on a single red cell, we can usually 
make out a fine, wavy, so-called molecular motion in it. This is 
quite different from the active amoeboid movements observed in 
dying cells, and from the rapid dancing of malarial pigment. 

(/) The familiar appearance of spines all- over the cells usuall}' 
called " crenation" need not be described here (see Fig. 24, p. 79). 

But it is the ver}^ earliest beginning of crenation that leads to 
mistakes, as when only one projection has been developed and that 
points toward the eye, so that a bright spot in the corpuscle is all 
we see. 

(g) Unless we disinfect the skin before puncturing we must be 
prepared to find in fresh preparations (1) oil drops ; ' (2) epithe- 
lium; (3) particles of " dirt " ; (4) small colorless motile organisms 
about 1 ,a in diameter (Mliller's "Haemoconien," see page 58). 

(h) We may make a rough estimate of the number of red cells 
present if Ave take care to spread the drop of the same thickness 
each time. The eye gets used to tlie ordinary look of a Avell-filled 
field of corpuscles and notices a look of thinness if any considerable 
anaemia is present. 

(^) The degenerative changes to be seen in normal blood after 
long exposure to the air, Avhich can get in between slide and cover, 
are described in detail later on. In pathological blood we may find 
these as soon as the blood is draAvn. 

' In some conditions the blood really contains fat {ride infra, " Lipaemia"). 



PHYSIOLOGY OF THE BLOOD. 51 



11. White Cells. 



(a) The ivhite or colorless cells are but little different from the 
red in color, the latter being so nearly colorless. We first notice 
them either b}^ their amoeboid movements, or because they are not 
moved by the plasma currents, but stand like a rock round the sides 
of which the current of red cells is broken. They are slightly 
larger in most instances than the red cells; but this difference 
shows less in the fresh specimens where the leucocyte keeps its 
spherical shape than in the dried and stained i^reparations, where it 
is usually somewhat flattened. Their shape is very irregular and 
their edges often look tattered. 

In some leucocytes the amoeboid motions are almost absent 
These are the smallest cells, and in them a single nucleus filling 
most of the cell can often be seen. They are much more nearly 
spherical and less irregular than the larger and more active cells. 

The large amoeboid leucocytes are more or less granular, and in 
certain -lights these granules look quite dark and are sometimes 
mistaken for bits of malarial pigment. This is especially true of 
the coarse granular cells seen occasionally; staining shows these 
large granules much more distinctly (=zeosinophile — see below, page 
61) ; cells of this type are the most actively amoeboid of all. 

{h') The most important point in connection with the leucocytes 
is their ratio to the red cells. This is estimated in fresh specimens 
not by any actual counting, but by reference to a standard fixed in 
the mind by study of normal specimens, so that any considerable 
increase of the w^hite cells is noticed at once Naturally we must 
not judge from any one part of the slide, as the distribution of the 
leucocytes may be unequal in different parts of it, 

111. Blood Flutes.' 

Unless the number of these elements is increased by some path- 
ological influence, we seldom notice them at all in fresh blood. 
This may be because we do not work quickly enough in preparing 
our specimen Hayem recommends that the cover-glass be laid 
upon the slide before the puncture is made; as soon as the drop 

' It is probable that the elements included under this heading comprise 
several different things. It is beyond the plan of this book to discuss their 
origin and significance, since they possess at present no clinical value. 



52 



CLINICAL BLCOOD EXAMINATION. 



emerges it is allowed to nm in between slide and cover by capillary 
attraction, thus avoiding contact with the air. ' The blood ])lates are 
irregularly shaped, very cohesive elements, about one-half the diam- 
eter of a blood disc, usually seen clinging together in masses like 
zoogloea. They are colorless and not amoeboid and look like debrl<. 

IV. FiJn-tn Si'fff'ork. 

After a specimen of fresli blood has stood for some time exposed 
to as nmch air as can creep in between slide and cover-glass, we 
begin to notice a network of fine straight lines in the spaces be- 




Fk; 



IJ(iiilt';iiix roniiatiou and Fibrin Network of Normal Blood. 



tween the corpuscles. Here and there these filaments seem to 
radiate from a centre wdiere irregular, colorless masses, apparently 
blood plates, are to be seen (Fig. 22). 

No stain is needed to demonstrate these fibrin threads, but a 
small-aperture diaphragm and very little light make them plainer. 



' This is a ver}' satisfactory way if we wish to see tlic corpuscles as fresh 
and unspoiled as we can. Put a cover-glass on a slide so that the edge of one 
corresponds with the edge of the other, and, holding them in this position 
with finger and thumb, put their superimposed edges into the side of the drop 
as it emerges. It Avill run in between them by capillary attraction. Blood 
plates stained by Wright's method are easily seen and their number may be 
approximately estimated. 



PHYSIOLOGY OF THE BLOOD. 



53 



Their only importance is that under certain pathological conditions 
the librin network is very much increased and helps us in the diag- 




FiG. 23.— Increased Thickness of Fibrin Network. 



nosis (Fig. 23). Hence it is of importance to be familiar with the 
ordinary closeness of the network in normal blood as a standard of 
comparison. 

For an account of the conditions of its increase see Chapter IX., 
page 114. 

Ayp:kage Diameter of Red Cells. 

The blood under normal conditions shows considerable variations 
in the size of its corpuscles in the fresh state as well as in stained 
specimens.' 

- A method of measuring, approximately accurate, and easilj' applicable in 
clinical work is the following : 

Using a camera lucida, trace on paper the divisions of a fine-stage microm- 
eter as seen under a one-twelfth oil-immersion lens; such micrometers are 
usually ruled to one one-hundredth of a millimetre. Approximate accuracy 
in our tracing can be obtained if the process is repeated till the divisions 
marked in successive drawings correspond accurately one with another. Care 
must be taken that the paper is flat upon the table beside the microscope, and 
not raised on a block or otherwise ; also that the part of the paper on which 
we draw should be perpendicularly under the centre of the mirror and not off 
to one side. When a drawing has been made with these precautions, we have- 
only to divide the space betw^een each of the lines in our drawing into ten 
equal parts, and %ve have a scale, each division of which represents 1 i-i as seen 



-54 CLINICAL BLWOD EXAMINATION. 

The following table (v. Limbeck) shows the results of various 
observers. 

Normal Limits. Average Diameter. 

Wehkcr diameter = 4. 5-9. 5 /^ 7 // 

Valentin 7 /^ 

Maliniu 7.7 // 

Hayem diameter = H-8.8 // . 7.5 // 

Mallasse/ 7.6 « 

Laache diametei" = 6-9 //.... 8.5 fi 

Bizzozero 7.075 // 

Gram diameter = 6.7-9.3 // 7.850 // 

Average = 7.5 // 

These differences depend partly on differences in the method of 
measuring (wet or dry), and partly on the fact that the age and 
conditions of nutrition in the persons selected make a difference. 
In the new-born, and to some extent throughout childhood, the 
normal limits of variations are Avider than in adults (3.8-10.5 //, 
Hayem). Sex appears to have no constant influence. 

The majority of any individual's red cells are certainly about 
7.5 ;/. in diameter, and this may accordingly he taken as our 
standard (Hayem counts twelve per cent under 6.G ,"., twelve per 
cent over 8 //, the rest 7.5 //.). 

XOUZVIAL ^lAIHEH OF THE EeD CeLLS. 

1. At the level of the sea and in adult life the normal number 
of red cells per cubic millimetre is about 5,000,000 for men and 
4,500,000 for women. This is frequently exceeded in vigorous, 
healthy persons; 6,000,000 is by no means rare among healthy 
young men, and higher hgures are seen occasional!}'. Thus Hewes ' 
in fift}' young medical students foimd an average of 5,809,000 per 
cubic inillimetre; of these fifteen exceeded 6,000,000, the highest 
heing 6,400,000, while the lowest of the whole series w^as 5,120,- 

under a one-twelfth oil-ininiersion lens, with the tube of the particular micro- 
scope used. To use our //-scale we have only to draw with the camera lucida 
any cell whose size we want to know, using always the same microscope, tlie 
same length of tube, and the same lenses, and having the drawing paper as 
before flat on the table and perpendicularl}' under the mirror. The drawing 
thus made is measured with the ^u-scale like any other object. 

With this method a cell can be measured in a few seconds and with suffi- 
cient accuracy {i.e., within 0.5,u). 

^ Transactions of the Boston Society of Medical Science, May 18th, 1897. 



PHYSIOLOGY OF THE BLOOD. 55 

000. Altitude above the sea. level raises the count invariably (see 
page 74). 

2. The influence of menstruation, childbirth, and lactation is to 
diminish the red cells temporarily, the amount of the diminution 
depending not only on the amount of blood lost but on the capacity 
of the individual organism for blood regeneration. At puberty, 
when sexual functions are being established, we expect lower counts 
than after the establishment of the function. Normal pregnancy 
does not affect the count of red cells. 

3. The count of red cells per cubic millimetre is raised by any 
cause inducing concentration of the blood, such as profuse sweating, 
and is lowered by the temporary dilution of the blood after large 
draughts of liquid. In these changes, which are always very tran- 
sient, the haemoglobin and specific gravity in a given drop are of 
course increased with the corpuscles. 

Vasomotor influences affecting the calibre of the peripheral ves- 
sels (hot or cold baths, exercise, etc.) may temporarily concentrate 
or dilute the blood by affecting the interchange of fluid between the 
vessels and the surrounding lymph spaces. By these processes the 
blood in the peripheral vessels may show an increase or diminution 
in the cellular elements, the haemoglobin and specific gravity corre- 
sponding to the greater or less concentration of the blood at that 
point (on these points see below, page 73.) 

Hayem noted that in young people especially the number of red 
cells varied considerably without any notable change in conditions. 

4. Influence of Nutrition on the Number of Red Cells. 

A. After ct meal, especially when considerable liquid is taken, 
the blood is temporarily diluted and hence the count of red cells 
per cubic millimetre is diminished (v. Limbeck, Eeinert). This is 
illustrated by the following case from v. Limbeck : 

Adult Male, Healthy. 

Red Cells. White Cells. Hasmoglobin. 

11:15 a. M 5,530,000 7,660 98 per cent. 

12 M. dinner. 

12:15 p.M 5,320,000 6,166 

1:15 " 5,480,000 8,500 

2:15 " .....4,733,000 12,000 

3 :15 " 4,872,000 14,000 89 per cent. 

4:15 " 4,720,000 10,830 89 



56 CLINICAL BLOOD EXAMINATION. 

As the white cells rise (diurnal variations, see page 91) the red 
fall. 

Fasting, by concentrating the blood, temporarily increases the 
number of red cells (400,000-500,000 increase after twenty-four 
hours' fast). 

B. General Nutrition. — Lean, muscular people have on the aver- 
age more red cells ]3er cubic millimetre than fat people (Leichten- 
stern, quoted by v. Limbeck), other things being equal.' 

As above said, fasting (by concentrating the blood) raises the 
number of red blood cells, so that it is not simply hunger that gives 
us the diminution in red cells commonl}' found in poorly nourished 
people^ but rather the influence of bad hygiene in the slums, etc. 

5. Seasons and the time of doij seem to have no influence in 
themselves. The same is true of rare and climate. The only ex- 
ception to this is reported in the work of E. Below,- who found in 
yellow-fever districts an average count of only 4,700,000 red cells 
per cubic millimetre and the diameter of the individual cell reduced 
to 5.9 // on the average (7.5 ,a = normal).^ 

6. i^afi>?ye.— Hayem noted a loss of from 500,000 to 1,000,000 
red cells per cubic millimetre in the blood of a number of farmers 
after a hard summer's work, the counts made in September having 
been compared with those of April and always found to be lower. 
Whether fatigue is the only cause of this diminution may be 
doubted. 

7. Age. — In the new-born the number of red cells is very high 
for a few days (7,000,000 to 8,800,000), but falls at the end of 
seven to ten days (see page 445). 

In the very old a certain degree of anaemia is, so to speak, physi- 
ological; but this, which like the plethora of the new-born is to be 
referred not to the fact of age but to concomitant influences, is b}- 
no means invariable. Schmaltz reports 6,766,000 red cells in a 
man of eight^^-one and 4,816,000 in a woman of seventy-four. 

XOEMAL XUMBER OF WhITE CeLLS. 

The figure usualh* given for adults is 7,500 per cubic milli- 
metre. This varies a good deal, according to the nutrition of the 

^ The influence of stasis in the obese, whose fat loads the surface of the 
heart, is to cause an apparent increase of red cells. 

2"Deut. Tropenhygiene," Berlin, 1895. O. Coblauz. 
^ See also under Anchylostomiasis, page 428. 



PHYSIOLOGY OF THE BLOOD. 57 

individual (see page 89) and also at different times of the day, 
owing to influences not explained- In animals a slight shock ' is 
sufficient materially to affect the count of leucocytes; 5,000 to 
10,500 may be called the normal limits. Romberg finds 9,058 as 
the average count in fifty-five healthy young women. There is, I 
believe, no evidence to show whether or not mental disturbances 
(fear, rage, emotion of various kinds) affect their number, but my 
impression is that they do Other causes of variation will be dis- 
cussed under Leucocytosis. 
t 

Blood Plates. 

The number of blood plates is variously estimated at from 
180,000-250,000 (v. Emden) to 860,000 (Keinp and Calhoun). 
They do not contain haemoglobin and show no signs of a nucleus. 
They are the chief constituents of white thrombi. Wherever they ' 
are diminished (e.g. , in haemophilia, purpura) clotting is apt to be 
slow, and there is reason to believe— 

(a) That their number is an index of lowered resistance of the 
red cells. 

(b) That whenever their number is much increased, thrombosis 
is likely to occur. In chlorosis, for instance, their number is in- 
creased and thrombosis is relatively common, while in pernicious 
anaemia they are diminished, and thrombosis rarely if ever occurs. 

Coagulation time outside the body depends largely on the amount 
of fibrin and is a wholly different phenomenon from intravascular 
thrombosis. This is of importance in connection with the use of 
gelatin injections to favor thrombosis in aneurisms. An increased 
rapidity of coagulation outside the body is no indication of success 
in such cases. Blood plates are increased in chlorosis and in many 
cases of grave anaemia. In the severer types of many infections 
(measles, erysipleas, malaria) they are diminished, and in malaria 
they are sometimes wholly absent during the fever. In pneumonia 
and tuberculosis they are normal or increased. In purpura and 
haemophilia they are sometimes much diminished or absent. 

The physiological limits of the amount of hcBmoglohi7i and of the 
specific gravity have already been mentioned. Under physiological 
conditions their variations follow those of the count of red cells. 

' Lowit: "Studien z. Physiol, mid Pathol, d. Blutes," etc., Jena, 1892 
Fischer. 



58 CLINICAL BLOOD EXAMINATION. 



MuLLEK's ^' Blood Dust." 

Millie r ' has described under the title of '' Haemoconien/' or 
blood dust, a constituent of normal and pathological blood not 
previousl}^ noticed. This consists of small round colorless granules 
about the size of the finest fat drops — or about 0.25-1 jj. in diameter, 
their size being very variable. They are highly refractile and 
have rapid dancing (molecular) motion, but no power of locomotion. 
They are insoluble in alcohol and ether, not stained by osmic 
acid, and take no part in the formation of fibrin. Stokes and 
Wegefarth,- who have confirmed jMiiller's observations, note that 
the " blood dust ^ can be seen much more clearly by the light of a 
Welsbach gas burner than by daylight. The latter observers pre- 
sent a body of evidence tending strongly to show that these bodies 
are the extruded griinules of neutrophilic and eosinophilic leucocytes. 
Granules apparently identical with them can be stained in fresh 
specimens with eosin or Ehrlich's triacid stain in a way apparently 
like that of the intracellular granules.^ They are also to be seen 
in pus and in hydrocele fluid. 

No special diagnostic or prognostic significance has yet been 
attached to them, though the work of Kanthack and Stokes renders 
them of great interest with reference to the problem of immunity. 



^ Centralbl. fiir allg. Path., etc., viii., 1896. 

2 Johns Hopkins Hospital Bulletin, December, 1897. 

2Nicholls: Phil. Med. Jour., February 26th, 1898. 



CHAPTER V. 

FINER STRUCTURE OF THE BLOOD. 

Appearances of Dried axd Stained Specimens. 

In cover-glass specimens prepared, and stained as above directed 
approximate ideas of the quantity of red cells, of white cells, and 
of haemoglobin can be formed, parasites and bacteria can be seen; 
the whole mass of evidence based on the finer structure of the 
leucocytes can be obtained only in this way. The appearances of a 
specimen of normal blood prepared in this way are as follows : 

Red Cells. 

1. With Wright's modification of Leishman's stain the haemo- 
globin stains pink or yellow according to the amount of decoloriza- 
tion with water. With Ehrlich's triple stain the haemoglobin takes 
up the orange G of the mixture, and in a properly heated specimen 
the red cells are of a brilliant yellow or pale orange tint. If over- 
heated they have a feebly stained, washed-out look, while if under- 
heated tlieu are more or less hrotcn or gray.^ 

The degree of pallor of the centres corresponds to the amount of 
haemoglobin in the corpuscles, and can be gauged much more accu- 
rately in stained than in fresh preparations. The color of the 
edges is not much affected by pathological changes, the centres 
being the test. But in cases with extreme poverty of haemoglobin 
the colored rim may be reduced to a mere shell and the rest may be 
almost completely colorless. The power roughty to estimate the 
amount of coloring matter in this way can be easily acquired. 

An approximate idea of the number of red cells may be formed 
by any observer who has learned to use a uniform technique in each 
case and to spread the blood of a standard thickness. 

^ This is a fruitful source of error. Many suppose that because their speci- 
mens come out too dark they must be "burnt," and so heat less. In fact the 
dark tint means that the specimen is not heated enough. 



60 CLINICAL BLOOD EXAMINATION. 

2. With Ehrlicli's mixture the blood plates do not stain at all. 
With Wright's stain they are colored dark Y)urple or red. 

White ('oKinscLES. 

In normal blood stained l)y either of the methods al)ove described 
we recognize the following varieties of white cells : 

1. Those known as '' jjolynuclptir^'' ox jjolijmorpUonnrb'dr neu- 
thi'ophilic leucocytes, whicli make up about two-thirds of all the 
white corpuscles of normal blood and constitute the vast majority 
of those found in ordinary pus. Stained by Wright's method the 
nucleus takes an intense navy-blue color, and a moderate amount 
of network structure is visible within it. With Ehrlich's stain the 
nucleus takes a much lighter blue color, and its edges are ill defined, 
so that it does not so easily catch the eye. It is very irregular in 
shape, and no two are just alike. One often sees two main portions 
with outlines about as irregular as those of the American continents, 
and joined by a filament as narrow relatively as the Isthmus of 
Panama. The different parts of the nucleus often seem to be 
wholly separated from each other, but this is very rarely if ever the 
case. Careful focussing brings out fine filaments joining the appar- 
ently separated pieces. The windings and twistings of the nucleus 
suggest comparisons to the letters Z, S, or E. 

In the protoplasm of the cell around the nucleus fine granula- 
tions can be demonstrated which take a variety of shades of pink 
with Wright's stain, and with Ehrlich's a violet or purple. They 
are very small and irregular in shape, contrasting with larger and 
more spherical granules of the eosinophile. Between them can be 
seen in most cases a pinkish stained background of cell substance. 
With the lower powers of the microscope they seem to fuse together 
into a diffuse pinkish or purplish mass. 

The term "neutrophilic" is not strictly accurate, since the gran- 
ules can be stained (though more faintly) with eosin, but they are 
most distinct when stained with a differential acid mixture like 
Ehrlich's "triacid," which contains both an acid and a basic dye. 
There is some evidence for believing that these granules have when 
young a basic affinity, gradually changing to an acid affinity as they 
mature.^ 

' In infectious diseases and grave -annemias the granules of the polynuclear 
cells may altogether lose their staining affinities or large oval basophilic dots 



Examination of the Blood. 



PLATE I. 



Fig. 1. Varieties of Leucocytes. 



Polymorphonuclear 
neutrophiles - 




® 



^j[— Myelocytes 



^<;f ^p^ Small Lymphocytes 



^ 



Large Lymphocytes 



Eosinophile 




.i5 W; 

»... «r '• ^(^^ Eosinophilic 

/"Myelocyte 



The IWalariai Organism. 



2 "v 






':t 



9 /; ^ 
4A ^=-*' 






7%^:0 



'^^ 



W 






Fig. 2. 



Fig, 3. 



R. C. Cabot fee. 



Lith. Anst. v. E. A. FTinke, Leipzig. 



PLATE T. 

Fig. 1. — (a) Poh/morpJtoniirlcdr ycKtropliilcs. Xotc the varioties in size 
and shape of o-ranules, tlie irregnilar stainih"- of the iiuelei. the light si)aee 
around them, their rehitively eentral position in the cell. 

(/>) Myelocytefi. Xote identity of granules with those just described; the 
even, pale stain of nuclei; their position near the surface (edge) of the cell. 
The two cells figured indicate the usual variations in the size of the whole cell. 

{c) Small Lyinphocytes. In the cell at the left note transparent protoplasm ; 
in tlie cell next to it note xery pale pink of protoplasm around nucleus which 
is deeply stained, especially at the periphery. The next cell has an indented 
nucleus; its protoplasm relativel}' distinct. The cell on the extreme right 
shows no protoplasm and is probably necrotic. In all note aMence of ffraiwles 
with tins stain. With basic stains a blue network appears in the protoplasm. 

{(J) Lurijc Lympliocytcs. Note pale-stained nuclei and protoplasm, irregu- 
larity of outline; indented nucleus in one. Everv intermediate stage between 
these and the ^^ small '^ h'mphocytes occui's, and the distinction between them 
is arbitrary. 

(c) Eosiiiophile. Xote irregular shape, loose connection of granules, their 
copper color, their uniform and relatively large size, and spherical shape. 

(/) Eosinophilir Mi/elocyte. Xote similarity to (h) ordinary myelocytes ex- 
cept as regards granules. Color of granules may be as in {e) ordinary eosin- 
ophile. 

All the above were stained with the Ehrlich triacid stain, and drawn with 
camera lucida. Oil-immersion objective one-twelfth and ocular Xo. iii. (Leitz). 

Fia. 2. — Malarial Parasites in Freslt {Unstained) Blood (Tertian Forms). 
N,]S, normal red corpuscles; 1, red cell containing hyaline body ; 2, 3, 4, 5, 
successive stages in the development of the parasite, shoAving acquisition of 
pigment; 6. 7, full-grown parasites, the corpuscle no longer visible; 8, begin- 
ning of segmentation; 9, segmentation. In 6 and 7 note brownish blur behind 
the pigment dots. Drawn as in Fig. 1. 

Fig. 3. — Tertian Parasite Htained with Eosin and Methyl Bine. The re- 
mains of the corpuscle containing the parasite stain pink, the parasite blue, 
and its pigment black. The stages of growth correspond with the numbers 
attached. Xote in Figs. 1, 2, 3, and 4 the shape of the parasite, shown better 
than in fresh specimen. 

[Owing to a mistake the cells in Fig. 3 are not drawn according to a single 
scale and their relative sizes must be disregarded.] 



FIXER STRUCTURE OP THE BLOOD. 61 

2. Li/nqjJiocytes. — With Wright's stain the nucleus, which is 
about the size and shape of a red corj)uscle, stains deep purplish blue 
(see Plate A). Around it is a narrow rim of protoplasm, which 
takes a robin's-egg-blue tinge. As a rule this rim shows no gran- 
ules, but occasionally a few blue or pink dots may be seen upon it. 
With Ehrlich's triple stain the nucleus of lymphocyte is colored 
very pale blue in the majority of instances, so that the cell often 
escapes notice in hast}^ differential counts. The protoplasm may be 
altogether unstained, or may be of a bluish tint, still paler than 
that of the nucleus (see Plate I). 

Cells of the type just described vary in size from that of a red 
corpuscle, or slightly smaller, up to two or three times that size. In 
the larger forms the nucleus may be eccentric or indented and the 
protoplasm rim wider. One often sees in the protoplasm of these 
forms pink, purple, or dark-blue granules, which are of various 
sizes, but usually scanty. Some of the large forms have a proto- 
plasm considerably darker in color than that of the small lympho- 
cytes, and at times the granules are so numerous that it is difficult 
to distinguish the cells from myelocytes. 

Occasionally the nucleus is more or less deeply indented at one 
side (Ehrlich's ^'transitional forms"). 

Within the group of cells just described most competent ob- 
servers distinguish two types, one called " lyviphocytes proper " 
(large or small) and the other ^^ large mononuclear cells ^ I think 
there is good reason to believe that this distinction is correct, but as 
no clinical importance has ever been attached to the so-called large 
mononuclear cells, and as they make up in the great majority of 
cases but a few per cent of all the leucocytes, it seems to me best 
at the present time to include them for practical purposes within 
the lymphocyte group. 

3. Eosinophiles. — With Wright's stain the nuclei are stained 
light blue or lilac, with a vague intranuclear structure. They are 
polymorphous, like those of the neutrophiles, but with a looser 
structure. The granules, which are about 1 ,a in diameter and 
roughly spherical or ovoid in shape, take with Wright's stain a 
brilliant eosin tint, while around them the protoplasm is very pale 
blue. With Ehrlich's stain the granules are copper-colored or 
brown, the nucleus is very pale blue, the protoplasm unstained. 

may appear anion S' the normal araniiles. ' (Ilirclifelt : Berl. Idin. Woch., Jul}' 
2-2(i. 1901.) 



62 CLINICAL BLO0D EXAMINATION. 

These cells are more easily injured by the technique of spreading 
the film than is any other variety of leucocyte, and are often found 
broken, their granules scattered about the fields. 

4. 3Iast Cells. — One of the striking features about Wright's 
stain is the prominence which it gives to the mast cells, which, with 
Ehrlich's stain, usually escape notice altogether. They are about 
twice the diameter of a red cell. Their nucleus has very vague 
outlines, but seems usually to be polymorphous. Over and around 
it are scattered granules larger even than those of an eosinophile 
and of an intense blue color, sometimes almost black. They may 
be very numerous, practically obscuring the nucleus, or scattered 
thickly about the margin of the cells. Occasionally they are dis- 
tinctly ovoid and plum-colored. 

Summing up, we find it most convenient to divide the leucocytes 
of normal blood into four varieties : 

1. Polynuclear or polymorphonuclear neutrophiles. 

2. Lymphocytes — large and small (including the so-called 
"large mononuclear'' forms and Ehrlich's transitional cells). 

3. Eosinophiles (polynuclear). 

4. Mast cells. 

Terms. 

No one can feel more unsatisfied with the terminology used in 
this book than the writer. It rests partly on a theory of the origin 
of the cells (" lymphocytes "), partly on the properties of the nucleus 
("polymorphonuclear"), and partly on affinities for aniline dyes 
(" neutrophile " — " eosinophile "). 

All that can be said for it is that it discards certain very mis- 
leading names like " splenocyte " (a term applied by some to the 
large lymphocytes according to the now exploded theory that they 
come from the spleen), or like "small mononuclear," to designate 
cells not rarely polynuclear. 

Origin of the Different Vnrieties. 
Two groups may be distinguished : 

(a) Poljmiorphonuclear 



I. The myelogenous group 
(from the bone marrow). 



neutrophiles. 
{b) Eosinophiles. 

(c) Mast cells. , 

(d) Large mononuclear cells 

(Ehrlich)? 



FINER STRUCTURE OF THE BLOOD. 63 

II. The lymphogenous group Lymphocytes of all 

(from adenoid tissue). sizes." 

Except within Group II. no transitions between the differ- 
ent varieties of circulating leucocytes are recognized. 

Normal Percentage of Each Variety. 

In the blood of healthy adults the proportions of the different 
varieties above described are the following : 

. j Small lymphocytes 30-30 per cent. 

^^^Large " , 4-8 

(5) Polymorplionuclear neutrophiles 62-70 " 

(c) Eosinophiles i-4 " 

(d) "Mast cells " ^Vi^ 

(a) In infancy the percentage of lymphocytes is much larger 
(forty to sixty per cent) and the polymorphonuclear neutrophiles 
are only eighteen or forty per cent. 

In a variety of debilitated conditions not usually thought of as 
definite diseases, the percentage of lymphocytes is comparatively 
large and that of the polymorphonuclear cells small. ^ The general 
vigor and health of the individual can sometimes be estimated 
simply from the leucocytes. Persons calling themselves well, but 
never vigorous or active, may show no more than fifty per cent of 
polymorphonuclear cells, the Ij'inphocytes running up to forty, 
fifty, or even seventy-five per cent. In an unmarried woman of 
twenty-nine, suffering from no discoverable organic disease, I found 
one day among 1,200 leucocytes 74.9 per cent of lymphocytes with 
only 25 per cent of polymorphonuclear cells. The total leucocyte 
count was 6,000 per cubic millimetre. Two weeks later the per- 
centages were normal, although no change had been observed in the 
patient's (debilitated) condition. She is now well and married. 

Not all cases of debility show this change, and we are not yet 
in a position to say under just what conditions it occurs. It cer- 
tainly is not peculiar to tuberculosis, as Holmes has supposed. Pre- 
sumably the conditions are such as decrease the functional activity 
of the marrow. 

(b) Changes in the percentage of neutrophiles will be discussed 
later. 

(c) The percentage of eosinophile's often changes in a way hard 

* This change is usually dependent on an absolute diminution in the mye- 
logenous cells. 



64 CLINICAL BLQOD EXAMINATION. 

to explain. Their increase or decrease in the circulating blood does 
not follow that of the polymoi'phonuclear neutrophiles — in fact is 
often inveisely i)roportional to it, and the eosinophiles may be 
markedly increased in a blood otherwise normal, for reasons wholly 
unknown to us. 

The eiasinophiles and " mast cells " may be pictured as compara- 
tive strangers, though not intruders in the circulating blood. They 
are thus intermediate between the regular inhabitants (lymphocytes 
and neutrophiles) and the variety next to be mentioned, which are 
real intruders — i.e., almost never found in normal blood. These 
are the 

Myelocytes. 

The larger portion of the leucocytes of the marrow is made up 
of mononuclear neutrophiles, a type of cell not yet described, and 
differing from any variet}' found in normal blood, although it has 
man}^ points of resemblance to the polymorphonuclear neutrophile, 
and is, in fact, the same cell in an earl}- stage of growth. I de- 
scribe it here because it is peculiar to no one disease and is 
an occasional visitor of the blood in various diseased conditions, 
and in conditions on tlie borderland between tlie jjathological and 
tlie phj'siological (starvation, muscular fatigue). 

The myelocyte (see Plate I. and Plate B.) is most easily recog- 
nizable if stained b}' Ehrlich's methods. With Ehrlich's triple stain 
it appears as a spherical cell nearly filled by a large, pale- stained 
nucleus immersed in neutropliile granules. One sees at once how 
little it differs from the large lymphocytes (simply in having gran- 
ules) and from the polymorphonuclear neutrophile (onl}' in the shape 
of its nucleus). I have called the granules neutrophilic, and this is 
true of the great nuijority of them in most cells. But as Ehrlich has 
recently pointed out, there is a great deal of variation in the staining 
affinities of different granules, side by side, in the same cell. In 
some granules (according to Ehrlich the j'ounger ones) " there is 
prominent a basoj^hile portion which becomes less and less marked as 
the cell grows older." Such granules take with Wright^ s stain a 
bluish tint. Others near them (older?) are violet, while others again 
are nearh' pink. In the polynuclear neutrophile these basophile affin^ 
ities are much less marked, but even in them considerable differences 
may be made out between the tints of adjacent cells and of adja- 
cent granules in the same cell. In size and shape the myelocyte 



FINER STRUCTURE OF THE BLOOD. 65 

granules are like those of the polyuuclear cell. The nucleus, by 
which we chiefly distinguish the myelocyte, shows none of the 
twists and turns characteristic of the polymorphonuclear neutro- 
phile, but is usually spherical or egg-shaped, and is in close contact 
with the cell wall for a comparatively large portion of its extent — 
i.e.., if egg-shaped it is placed eccentrically. 

Not infrequently the nucleus shows signs of old age (vacuoles) 
or of mitosis, for occasionally we find two nuclei at the poles of 
the cell. 

Size of Myelocytes. 

All the older accounts of the myelocyte speak of it as a very 
large cell, the largest variety of leucocyte ever seen in the blood. 

This is true of many of them; diameters of 18-21 // are not un- 
common, but we also find them of every other size down to 10-11 /x 
diameter — that is, down to the size of a lymphocyte. This holds 
both for the myelocytes in the circulating (leuksemic) blood and for 
those in the marrow. No distinction from other varieties of leuco- 
cyte can be based on size alone, unless we say their average size is 
greater than the average size of the leucocyte. Perhaps the follow- 
ing table may be of interest : 

Average diameter of 100 myelocytes = 15.75 ^. 

" " " 100 polymorphonuclear neutrophiles = 13.50 /i. 

" " " 100 " large " lymphocytes = 13 [i. 

" " " 100 eosinophiles = 12 //. 

" " " 100 " small " lymphocytes = 10 fi. 

" " " 100 red corpuscles (normal) = 7.5 fi. 

Eosinophilic Myelocytes. 

Under the same conditions which favor the appearance of the 
ordinary (neutrophilic) myelocyte, we often find a small number of 
cells identical with them in all respects, except in possessing eosino- 
philic in place of neutrophilic granules. Such cells are found in 
abundance in the marrow, and this fact, together with the resem- 
Ijlance to the ordinary myelocyte both in morphology and in the 
conditions of their occurrence, seems to me to justify the term 
eosinophilic myelocyte. In them as in all myelocytes there is a 
wide variation between the staining affinities of different granules, 
some being much darker than others. 
5 



6& CLINICAL BLOOD EXAMINATION. 

So far I have described the tt/pe call of eacli variety. As we 
should expect, atypical forms are numerous. Some of the com- 
moner ones are as follows : 

I. Degenerated Leucocytes. 

Frequently in leukaemia and occasionally in other conditions 
one sees leucocytes apparently moribund. That they are not ordi- 
nary artifacts is shown by the fact that they are not found in nor- 
mal blood treated by the same technique that reveals them in the 
blood and in hardened blood clot of leukaemic cases, as well as by 
the fact that Botkin and others have produced similar appearances 
by keeping the leucocytes a few days in an aseptic state. 

The commonest forms of degenerated leucocytes are : 

1. A homogeneously stained mass looking like a washed-out, 
structureless nucleus that has lost its protoplasm and become ragged 
at the edges (karyolysis). 

2. The same intensely stained. 

3. Vacuolization of the nucleus or of the protoplasm. 

All these forms of degeneration affect chiefly the lymphocytes 
and large mononuclear forms. In the granular leucocytes we see 
all stages of breaking up; the granules are scattered about the field 
and the nucleus is pale, structureless, and deformed. 

II. Transitional XkithophiivES. 

Cells on the borderland between the " marrow cell " and the 
"polymorphonuclear leucocyte," the nucleus having some of the 
characters of each variety (see below, page 103). 

III. Turck's "Stimulation Forms.'' 

These cells are also described by Engel as " mononuclear cells " 
and very recently by Weil as " non,granular myelocytes." 

Weil's description conveys the salient points in the appearance 
of this cell. It looks like a myelocyte whose granules have been 
fused into a smooth homogeneous band of color around the single 
spherical or ovoid nucleus. The protoplasm is always homogeneous 
and deeply stained; there is, how^ever, a good deal of variation in 
the tint in different cells. In some it is purple, in others violet or 



FINER STRUCTURE OP THE BLOOD. 67 

brown. In leuktemia they are often counted as myelocytes or as 
large lymphocytes by unpractised observers. 

They appear in various diseases associated with stimulation of 
the hone man'otv, i.e., grave anaemia and all conditions associated 
with leucocytosis (see below, pages 102-103). 

Other rare varieties will be mentioned under Leukaemia. 



PART in, 

GENERAL PATHOLOGY OF THE BLOOD. 



CHAPTER YI. 

UNEQUAL DISTRIBUTIOX OF BLOOD— POLYCYTHEMIA— DILU- 
TION AND COXCKXTRATION OF THE BLOOD. 

1. UiicqiKil Dlsti'lhution. 

How far is tJie single drop used for l)lood examination typical 
of the whole? 

It has been experimentally proved that specimens of the blood 
of the smaller venous and arterial twigs do not differ from each 
other materially in corpuscular richness. Capillary blood is slightly 
richer in corpuscles than that either of veins or of arteries. But as 
capillary blood is everywhere of the same corpuscular richness, Ave 
may consider one capillary network or set of venules as typical as 
another, provided our technique is good — that is, provided lymph 
is not squeezed into the drop by strong pressure. It is indifferent, 
therefore, so far as accuracy is concerned, whether the drop of blood 
be obtained from one or another part of the body. All standard 
estimates of the number of corpuscles per cubic millimetre of nor- 
mal blood refer to capillary blood. 

2. Local or Perqjheral ^oiycythcemia. 

So far we are speaking of normal conditions. It is a familiar 
fact, however, that the vessels of a given part of the body can be 
overcrowded with blood, e.g., by the use of an Esmarch bandage. 
A drop taken from such a part would certainly not be typical. 
Now as the same effect can be produced by a variety of diseases, 
under these conditions we must modify considerably any inferences 
made from examination of a single drop. 

Such conditions, entailing a false polycythaemia or apparent in- 
crease in the number of corpuscles, are : 



GENERAL PATHOLOGY OF THE BLOOD. 69 

Any disease involving either («) general cyanosis or (b) cyanosis 
of the part from which the drop of blood is drawn. 

(a) General cyanosis results from cardiac insufficiency (valvu- 
lar or parietal disease of the heart itself, blocking of the lung 
circulation by emphysema or thrombosis), from insufficient aeration 
of the blood (pneumonia, congenital malformation of the heart), 
interference with the heart's action by pressure of tumors, effusions 
(pericardial, pleural, peritoneal), or enlarged organs (liver, spleen), 
or from vasomotor disturbances. It is evident that some of these 
conditions {e.g., congenital heart disease) may not involve any 
peripheral stasis at all, and in the absence of this it is not easy to 
account for the increased number of corpuscles in the drop. What- 
ever the explanation may be, there is no doubt of the fact that gen- 
eral cyanosis from any cause whatever produces an increase of cells 
in a drop such as we usually examine. 

The cases of cyanosis Avhich I have classed under " cryptogenetic 
polycythaemia '^ (for want of a better name), cases in which, in the ab- 
sence of disease in any organ, the skin and mucous membranes are 
persistently and markedly bluish, are not very uncommon. I have 
seen three such, all in stout, elderly women. In one the cells in a 
drop of blood from the ear, finger, or toe were more than dovhlp the 
normal number (see page 71.) 

(h) Local Cyanosis. — The pressure of a tumor, or any other 
hindrance to the circulation of any part, may give a similar increase 
in the number of corpuscles in a measured amount of blood from 
that part. In paralyzed patients the count may be higher on the 
paralyzed side. In markedly cyanotic patients the count of red cells 
may be notably above normal, and we must make allowances. Error 
is more likely to arise when we have cyanosis in a person whose 
blood is poor in red corpuscles. The combination of these two fac- 
tors may give us a normal blood count and lead us to overlook the 
anaemia. Thus a person might have really a severe anaemia and 
yet the count of red cells be actually above the normal. This 
element of stasis should never be lost sight of. Many high counts 
reported in pneumonia or hysteria are to be explained b}^ abnor- 
malities not of prodtiction or destruction but of distribvtion of the 
blood cells. 

With these exceptions the drop of blood taken at the periphery 
is typical. We have next to consider some geneval conditions 
under which a person's whole blood may be inferred to be abnor- 



70 CLINICAL BLOOD EXAMINATION. 

iiial from tlie findings in a drop taken from the p(M-ipherv. Consid- 
eration of special diseases will follow latei-. 

Temporary increase or diminution in tlie amount of fluid within 
tlie vessels can be brought about not only by a change in tlie m»'- 
chanical conditions of pressure and osmosis, but by any influence 
affecting the tone of the peripheral vessels. We liave then : 

Teriipordfj/ Serous Plethora or hiliitian of fjte Blood. 

(a) From transfusion of fluid in laige amounts or its ingestion 
by mouth or lectum. 

(^) From decreased bhxtd jjressure, as in acute failures of com- 
pensation in cardiac disease, 

(c) From vasomotor dilatation. 

As an example of this last Grawitz reduced tlie specific gravity 
of the blood from 1041 To 1038.7 within eight minutes by the inha- 
lation of nitrite of amyl. This decrease of specific gravity can only 
mean an increased amount of watery constituents in the blood, as 
there was no evidence of any destruction of the heavier elements of 
the bloodj and only water (and chlorides) pass through the vessel 
walls easily. In the above case the specific gravity was again at 
1041 within a few minutes. 

Pol i/ciftho'ii} id . 

The red-faced persons popularly known as "full-blooded" show 
no abnormalities in their blood discoverable by any means of inves- 
tigation known to us. The condition is probably dependent on the 
presence of a ricli capillary network near the surface of the skin, or 
on a dilatation of individual venules and arterioles at the periphery. 
Such a person may be markedly anaemic without any considerable 
changes in the color of the face. The fact that people of such com- 
plexion often end their lives with a ruptured cerebral artery is due 
presumably to the circumstance that *'high living" produces in the 
same individual dilated peripheral capillaries and weakened arterial 
walls. • 

Examples of what seems more likely to be a true polycythsemia 
are as follows : 

(a) In cases of severe anaemia which recover, the blood regener- 
ation may attain such vigor that the number of red cells shoots tem- 
dorarily up above normal, even as high as 7,700,000. 

(?>) The same condition can be temporarily produced by trans- 



GENERAL PATHOLOGY OF THE BLOOD. 



71 



fusion of actual blood from one individual to another. It lasts but 
a few days as a rule. 

(c) Some cases occur without any known cause. In one such 
case which came to autopsy (death from cerebral hemorrhage) the 
internal organs were as deeply engorged as the periphery of the 
body. Similar cases — often associated with splenic enlargement — 
have been reported by Vaquez, Osier (Trans. Assn. American Phy- 
sicians, 1903), by McKeen {Boston Med. and Surg. Jour., June 
20th, 1901), by Saundby and Eussell {Lancet, 1901, i., p. 515) and 
by Hall {Amer. Med., June 27th, 1903). The cases of the follow- 
ing table are apparently of this type. 

Table I. — Ckyptogenetic Polycythemia, 



Age. 


Sex. 


Red cells. 


White 
cells. 


Haemoglo- 
bin. 


Remarks. 


29 




8,484.000 


15,000 
17.600 


a5 


February 5. Polynuclear, 84.6 ; lympbo- 
cytes, 13.8 ; eosinophiles, 1.6. 

February 8. Polynuclear, 90,4; lympho- 
cytes, 8 ; eosinophiles, 6 ; myelocytes, 1. 


56 




6,240,000 


10.000 


65 


First day. 






4,680,000 


5,600 


70 


Eighth day. 


5!^ 


F. 


11.352.000 


8,300 


105 


December 6. 






9,360,000 




105 


December 7. After walking. 






10,060,000 


11,700 p.c. 


110 


December 11. 






10,230,000 


8.800 


110 


December 17. Polynuclear, 77.25 ; lympho- 
cytes, 18.75; eosinophiles, 2.75; myelo- 
cytes, 1.25 ; microblasts, 2 ; normoblasts, 
2. Few mast cells. 


*^ 


M. 


8,484.000 


17,600 




Polynuclear, 90; lymphocytes, 8 ; eosino- 
phile. 1 ; mast cell, 1. 



The polycythaemia of the new-born, of high altitudes, and of 
phosphorous poisoning will be discussed later. 



Concentration of the Blood. 

It is obvious that influences opposite to those producing tempo- 
raiy full-bloodedness will produce temporary lack of fluid within 
the vessels. So acute diarrhoea, purgation, deprivation of liquids 
(as in starvation), rapidly accumulated serous effusions, profuse 
vomiting or sweating (by skin and lungs) produce a temporary con- 
centration of the blood hy draining out its diffusible elements (water 
chiefly) (see Table II.). All these influences are transitory. More 
permanent drains on the system, like chronic diarrhoea, diabetes 
insipidus or mellitus, or long-standing suppurations, show no evi- 
dence of lessening the volume of blood in the vessels. They drain 



72 CLINICAL BLOOD EXAMINATION. 

albumin out of the serum and corpuscles and so deorease the weight 
of the blood (see below, page 78), but the blood volume is not 
changed. Indeed, any influence has to work very quickly in order 
to concentrate the blood, for in an astonishingly short time the 
other tissues repay the vessels their loss of fluid and the normal 
blood volume is restored. 

The same temporary effects can be produced by influences 
constricting the vessels (cold, pain, suprarenal extract), and a 
concentration of the l)lood results whicli lasts a few minutes or 
hours. ^ 

In all these interchanges of contents between the blood-vessels 
and the other tissues it is, as above said, the watery elements chiefly 
that change. The red cells are not affected by the give-and-take of 
the vessels and tissues, and although cold produces in the peripheral 
circulation an increase in the number of white cells greater than 
can.be accounted for by simple concentration, the weight of evidence 
seems to be against any new production of cells and in favor of a 
change only in distribution, the white cells accumulating at the 
periphery. 

Now as the number of cells is not affected by these temporary 
variations in the volume of liquid within the vessels, it follows that 
the number to be counted in a cubic millimetre, though typical of 
the whole blood at that tiiue, is not to be reckoned from in the 
ordinary way. For example, after a severe diarrhoea or in phthisis 
after a night-sweat the Idood may be temporarily so concentrated 
that we find 6,000,000 or more red corpuscles per cubic millimetre. 
Under normal conditions of the blood mass we should infer from 
such a count that the body contained one-sixth more red corpuscles 
than usual. Here obviousl}' it means only (if ansemia is absent) 
that the blood mass is reduced one-sixth by concentration. It is 
only in such sudden reductions of blood volume that we can meas- 
ure the amount lost by this method. Long-standing causes of 
drain on the plasma might at any time act as destroyers of red cor- 

' Oliver has shown recently (Lancet, June 37th, 1896) that any influence 
causing rise of blood pressure will slightly concentrate the blood. Thus rais- 
ing the arm over the head and holding it there by muscular effort slightly 
concentrates the blood in that arm. Electrical stimulation or massage of the 
arm has the same effect. Lowering blood pressure, as when the arm is sup- 
ported passively over the head, dilutes the blood. This confirms the results of 
MitcheU (Med. News, May, 189.S) and of Cheron (Comptes Rend, de I'Acad. 
d. Sciences, 1896, No. vi.). 



GENERAL PATHOLOGY OF THE BLOOD. 78 

puscles as well, through the changes in the nutritive fluids in which 
they live. 

Further, it is only when we know the number of corpuscles just 
before the sudden drain on the plasma conies that we can measure 
the amount of plasma lost by the amount of apparent increase in 
the red cells. Stasis and any other cause that heaps up corpuscles 
at the periphery must also be excluded before we can judge of the 
loss of plasma in this way. 

The conditions of an abnormal concentration of the blood are 
those already alluded to as temporarily sucking away its watery 
constituents, namely : 

(a) Watery diarrhoea, especially in cholera and other acute dis- 
eases accompanied by diarrhoea. 

(h) Large and rapidly accumulating serous effusions (slow ac- 
cumulations would give time for the blood to take up water from 
the tissues and make up for its loss). 

(c) Profuse sweats.^ 

(d) Persistent vomiting or starvation of liquids (see Table II.) 

(e) Increased blood pressure (exercise, massage, electricity). 
Blood already lacking in red cells, if suddenly concentrated by 

such a loss of fluid, might deceive us into supposing it normal, 
because the number of cells in a cubic millimetre might be normal. 
In the p7'esence, therefore, of any such reason for concentration of the 
blood, we should always modify our ordinary methods of inference 
from the hlood count. For example, v. Limbeck records a case of 
hepatic cirrhosis with ascites in which before tapping the ascites 
the count of red cells was 3,280,000 ]per cubic millimetre. Within 
twenty-four hours after tapping there were 5,160,000 cells per 
cubic millimetre, the reaccumulation of the ascitic fluid going on so 
fast that the blood was unable to adjust itself and became overcon- 
centrated. A careless observation might have inferred a great gain 
in the corpuscular richness of the whole blood, when in fact not a 
corpuscle had been gained, and those present had probably grown 
poorer in albumin. 

1 Mayer (Zeitsch. f. dietet. u. phys. Therap., 1902, vol. vi., Hft. 7) finds that 
hot-air baths produce a transient increase in the haemoglobin and in the leuco- 
cytes. Hot-water baths had no effect on the leucocytes and slightly dimin- 
ished the haemoglobin. 

The combination of hot baths and hot drinks produces in children, accord- 
ing to Hannes (Centralb. f. in. Med., 1901, p. 823), a slight leucocytosis last- 
ing about an hour. 



74 



CLINICAL BLOOD EXAMINATION. 

Table II.— Starvation. 



Case. 


Age. 


Red cells. 


White cells. 


Haemo- 
globin. 


Remarts. 


1 

2 


23 
2 


12,000,000 
8,780,000 


10,000 


120 4- 


Stowaway . Ten days without food . 
Two weeks' starvation after caustic 
potash stricture of gullet. 



It remains to speak of two other conditions in wliich what ap- 
pears to he a true polycythsemia is found : 

1. In persons living at high altitudes. 

2. In persons suffering from phosphorus or C'O poisoning. 

1. Tln> Blood in H'ujh Altitudes. 

The polycythsemia of those living at high altitudes increases the 
higher one goes. Koppe ^ gives the following table : 



Place. 



Christiania. . . , 

Gottingen 

Tubingen 

Zurich 

Auerbach 

Reiboldsgriin . . 

Arosa 

The Cordilleras , 



Height above 
sea level. 



O 

148 metres 

314 " 

414 " 

425 " 

700 " 

1,800 " 

4,392 " 



Red cells. 



4,974,000 
5,225,000 
5, 322, 000 
5,752,000 
5,748,000 
5,900,000 
7,000,000 
8,000,000 



Author. 



Laache. 
Schafer. 
Reinert. 
Stierlin. 
Koppe. 

Egger. 
Viault. 



This change takes place within two weeks of the time of taking 
up residence in a high place, and independent of any change in diet 
or manner of living; even within twenty-four hours there may be a 
gain of 1,000,000 red cells per cubic millimetre. Phthisical pa- 
tients' blood is more affected than that of healthy persons. Ani- 
mals show similar changes. The haemoglobin is also inconsiderably 
increased, although it lags somewhat behind the corpuscles. Solly 
\Phil. lied. Jour., 1900, vol. i., p. 1074) reports that the increase 
so marked in newcomers partially disappears after two or three 
years' residence, while the blood of natives of the same high alti- 
tude is midway between normal and that of persons who have lived 
there but a few years. 

The corpuscles are often deformed and undersized during the 



^Mlinch. med. Woch., 1890. No. 41. 



GENERAL PATHOLOGY OF THE BLOOD. 75 

earlier weeks of the change; but their volume, as determined by 
the hsematocrit, is not increased, and nucleated forms are not found. 

Later the poikilocytes and microcytes vanish and the hsemoglo- 
bin percentage rises so as to correspond with the increased count of 
red cells. 

On returning to low land, the blood returns within a short time 
to its normal condition. 

Many explanations have been offered for this interesting phenom- 
enon, the most reasonable, I think, being that which considers it a 
vasomotor phenomenon, due to lowered barometric pressure. 

^. Phosphorus and CO Poisoning. 

The polycythsemia of acute phosphorus poisoning may reach as 
high as 8,650,000. This may be partly explained by concentra- 
tion due to the occurrence of vomiting; but in some cases the in- 
crease seems out of proportion to the amount of vomiting. 

With illuminating-gas poisoning there is usually no vomiting to 
speak of, and the cause of the marked increase in the red cells is un- 
known. \^on Limbeck in two cases of CO poisoning showed respec- 
tively 6,630,000 and 5,700,000 red cells. Mtinzer and Palma ^ 
record 5,700,000. The white cells are also increased (see page 413). 

^Zeit. f. Heilk., vol. xv., p. 1. 



CHAPTER VII. 

ANEMIA AND HYDREMIA. 

1. ANvEMIA. 

Definition. — A deficiency in corpuscle substance, i.e., a deficiency 
in red corpuscles, in haemoglobin, or in both,^ with or without 
changes in the total volume of the blood. 

It is important to bear in mind that the color of the skin is not 
a safe guide in judging whether a person is ansemic. 

The most striking example of the fallacy of judging of anaemia 
by the color of the skin and mucous membranes is in the so-called 
^^ tropical ancemia.^^ Practically all persons belonging to white 
races who take up their residence in the tropics acquire after a 
time an extreme pallor of the skin and mucous membranes, and 
this appearance has usually received the title of ''tropical anaemia.'" 
It turns out, however, from the careful studies of several different 
investigators, that the blood of such persons shows absolutely no 
anaemia or other variation from the normal." 

We are to judge of anaemia, then, solely b}' the blood exami- 
nation. 

Distinction between Frimary and Secondary Ancemia. 

In one sense all anaemia is secondary. It is due to some cause, 
a symptom in a chain of events. But in some cases we know the 
cause and in some we do not. 

(a) Primary ancemia is that in which the causal factors are 
either entirely unknoivn or are 'apparently insvfiicient to produce so 
severe a disease. This division, like most of our statements about 
the blood, is a rough-and-ready one, held provisionally until a bet- 

^ This is a clinical definition and makes no attempt to go to the root of the 
matter. I have little doubt that chemical or other changes in the serum are 
the cause of the corpuscular changes, which only mirror the deeper disease. 
But these chemical changes are as yet so little understood that we have to 
judge of their presence chiefly by their effect on the corpuscles. 

2 So far as present methods of examination go. 



ANEMIA AND HYDREMIA. 77 

ter classification is discovered. It has a certain utility if not used 
with any less simple meaning than that given above. 

There is no good evidence that there are any primary diseases 
of the blood-making functions. A case of secondary anaemia is one 
in which we have an obvious cause such as hemorrhage or malaria 
for the loss of corpuscle substance. Eemove the cause and the 
anaemia ceases. Sometimes, however, after removal of the cause, 
e.g., after cure of a case of syphilis, the anaemia set agoing by the 
syphilis persists. On the other hand, there are few patients with 
" primary " anaemia who cannot recall some event in their past lives 
sufficient to account for a certain grade of ancemia (e.g., a nervous 
shock, a hemorrhage, an attack of tertian malaria). Yet if the 
anaemia that occurs after so slight a cause is of the pernicious or 
fatal type, we may fairly call it ^^ primary .^'' By this we mean 
that though the " cause " assigned might produce some anaemia, it 
was not sufficient to produce this fatal anaemia and has presumably 
little or no connection with it. "Primary" means not the absence 
of any cause of anaemia in the history, but the absence of any suffi- 
cient cause so far as is known. 

An attack of tertian malaria or a history of bleeding piles does 
not cause fatal anaemia in 999 out of 1,000 people who have such a 
history. In the 1,000th it is a case of post hoc and not propter hoc. 
Given the unknown cause that does lead to " primary " anaemia, and 
it might be that a pregnancy, a nervous shock, or the presence of 
intestinal parasites would act as the straw that breaks the camel's 
back; but the important causal factor is the unknown factor. Evi- 
dence is accumulating in support of Hunter's view that pernicious 
anaemia is due to excessive blood destruction produced by toxic sub- 
stances absorbed from the gastro-intestinal tract. Chlorosis is now 
generally believed to be a disease representing defective blood 
formation. But we are still in the realm of theory in these matters. 

It is true that in the majority of cases we can tell from the 
blood examination alone whether a case is without known cause 
(= "primary") or symptomatic (= "secondary"). But there 
appear to be enough exceptions to this rule to make us cautious 
about stating it as a law. 

r p • _ j Chlorosis. ( To be discussed under Special 

Anemi\ = J ^^^^"^~ ' ^^^'^^^^^"^^^^"^^^^•l Pathology of the Blood, 
^ ' ' ( Chapter VII. 

Secondary. 



78 CLINICAL BLOOD EXAMINATION. 



Serotiflori/ A ncpmia. 

I. First Stage. — I defined antemia above as o diminution in 
corpuscle substance. In the milder types of this condition the num- 
ber of red corpuscles is not diminished at all, but the individual 
cell is small, pale, and of light weight, through loss of nitrogenous 
matter. This is appreciated : 

{a) As a lack of coloring matter. 

{b) As a lowering of the specific gravity. 

In the mildest grades of secondary anaemia there are no further 
changes. 

The lack of coloring matter is usually not present in every cell, 
as is seen in the stained specimens. Some are very pale at the 
centre, while others are well stained. 

II. Second Stage. — Usually the next changes to appear are, like 
those already mentioned, qualitative, the number of red cells still 
remaining normal or approximately so. 

The individual cell as seen in fresh preparations is more or less 
deformed and varies from its normal diameter, dwarfed forms usu- 
ally being commoner than the giant forms. These variations in 
size and shape are sometimes termed "poikiloci/tosis,"- and the 
dwarf and giant forms are called respectively microcytes and 
macrocytes. 

Maragliano ^ has included the above changes, together with others 
about to be described, under the heading of 

Necrohiosis In the red coipuscles, attributing them to a patholog- 
ical condition of the serum. 

The changes united under this heading may be divided for con- 
venience' sake into 

(<z) Endoglobular changes. 

(h) Poikilocytosis and crenation. 

(c) Changes in staining properties. 

{d) Changes involving motility in the corpuscle as a whole, or 
in parts of it. 

(e) Decrease in the average diameter of corpuscles with loss of 
the power to form rouleaux. 

All these changes may be watched in normal blood outside the 
vessels, as necrosis gradually comes on from contact with the air. 

^ XI. Cong. f. Inn. Med., Leipzig, 1892. 



ANJEMIA AND HYDREMIA. 



79 



Under pathological conditions the same changes may occur outside 
the body, but more quickly than usual (as other diseased tissues 
decompose more quickly after death than those of a sound man sud- 
denly killed), or inside the body, 

(a) Endoglobular Changes (see Fig. 24, «). — These consist in 
the appearance of clear hyaline spaces of various shapes within the 
corpuscle, round triangular, rod-shaped, etc. In the fresh speci- 
men they change their shape rapidly and continually; in dried and 
stained specimens they ap- 
pear as sharply outlined 
light spaces in the corpus- 
cle. In normal blood these 
changes occur after thirty to 
seventy minutes outside the 
vessels. In some pathologi- 
cal conditions specimens 
show them the instant the 
blood is collected, and pre- 
sumably they were present 
before it left the vessels. 

(h) Crenation and Poiki- 
locytosis (Fig. 24, ^).— What 
we know as crenation in the 
corpuscles is probably the 

same sort of process which, occurring within the vessels, we call 
poikilocytosis. A lump rises at one or more points in the corpuscle, 
becomes more pointed, and gradually the whole cell acquires amoe- 
boid motions, assuming in succession the various shapes with which 
we are familiar in poikilocytes. Hayem has minutely described 
four types of motion in the red cells of anaemic blood. 

1. General amoeboid motion of the whole cell. 

2. Vermicular motion of flagella-like prolongations. 

3. Oscillating motions, especially in small light cells. 

4. Pseudo-parasitic motion. 

(c) The pointed projections may break off and move about ac- 
tively in the plasma. These motions, as well as the preceding 
amoeboid movement of the whole corpuscle, are to be explained as 
irregular contractions of the necrobiotic protoplasm, similar in a 
general way to the actions of a hen after its head is cut off. These 
motions are not to be confounded with the finer Brownian or " mo- 




FiG. 24.— Degenerative Changes in Red Cells. 



80 



CLINICAL BLOOD EXAMINATION, 



leculai- " movement to be seen in any healthy cell. The small bits 
broken off (Fig. 24, c) are doubtless the dwarf cells seen in dried 
and stained preparations. Curiously enough, these fragments tend 
again to assume the biconcavity characteristic of normal cells, as a 
drop of fat breaks into smaller but similar drops. 

(d) Oval Sha2)e. — In a great many cases of pernicious anaemia 
and some other forms of anaemia there is a marked tendency to 




Fig. 35.— Elongated or Oval Corpuscles in a Case of Pernifious Ana?mia. 

oval shapes in corpuscles not otherwise considerably deformed. 
Even in normal blood I think there are a small number of oval 
forms, and in anaemia this number may be greatly increased till, 
as in Fig. 25, we get all the cells elongated. The same appearance 
can be produced by roughness in spreading the blood, but in such 
case the deformed corpuscles all point one way. 

(e) Changes in Staining F7'operties. — Normal red corpuscles 
have affinity chiefly for acid stains. Influences like those which 
lead to the alterations in. shape and size above described may alter 
the staining properties of the cell as well, so that it takes up two 
or three colors (according to the number present in the stain), 
either diffusely or irregularly, some parts of the cell taking color 
differently from others. In lead poisoning, for example, minute 



PLATE A. 

Fto, 1. — III, ///. etc., Mc\s^al<)l)lasts, somo with polycliiomatopliilic proto 
plasm, some with degenerating nuclei (karvolysis). 

mi, mi, Microblasts. 

n. Normoblast. 

/, " Free " nucleus. 

h, Blue cell {i.e., basophilic er^'throc^yfc) with nuclear remnant. 

r, Ring 1)0(1}' in red-stippled (Mythrocytc. 

-s, Blue-stippled erythrocyte. 
Fig. 2. — m, m, etc., Myelocytes. 

J), p, etc., Polynuclears. 

t, t, Transitional neutrophiles. 

I, Lymphocyte. 

n, n. Normoblasts. 

me. Eosinophilic myelocyte. 

h, ]\Last cell. 

6, Eosinophile. 



Examination ofthe Blood. 



Plate A. 




P 



/ 




S 



« 




Mary W Rowley, del . 



Fig.l 



Red cells,- nulcealed, deformed or abnormallj stained. 
(Vl^ight's TTiodificatioTL of LeislmaanS stam.) 




Tig. 2 . MyzLO GENOUS liUCAEMIA. 

^ (^^'ft■ig■ht's modification of LeistimaTT^ stam.) 



Geo.HWa:ker L Co.,Lit>i„ 



ANEMIA AND HYDREMIA. 81 

bits of the red cells become basophilic, so that the cell presents, 
with appropriate staining, a stippled look. The same change 
occurs in pernicious anaemia and occasionally in other varieties of 
anaemia. This has been termed a ^^ polyclu^omatophiltc " or degen- 
erative change. Some observers have supposed it to be rather of 
the nature of regeneration^ believing that the cells take color in this 
unorthodox way because they are half-developed.^ 

(/) In many secondary anaemias, especially in those associated 
witl'i inflammations, the average diameter of the Cells is lessened, 
and the rouleaux are not formed.'^ 

(7) Cells may lose their haemoglobin altogether, leaving only 
the shell of the corpuscle behind (see Fig. 24, d). 

All these necrobiotic changes are characteristic of the severer 
grades of secondary anaemia, such as occur in cancerous cachexia, 
phthisis, nephritis, etc. 

III. Third Stage. — Here the number as well as the quality of 
the red cells begins to suffer. So far I have mentioned only the 
qualitative changes in secondary anaemia and have purposely made 
these changes more prominent than the actual diminution in the 
count of red cells, because it is only comparatively rarely and in 
very marked cases that the diminution in corpuscles is consider- 
able. The blood characteristic of most cases of secondary anaemia 
is one in which the number of red cells is approximately normal. 

The important exceptions to this rule are : 1. The anaemias of 
infancy and early childhood. 2. Large hemorrhages (soon after 
their occurrence). 3. Malaria. 4. Acute septicaemia. 

The direct and rapid destruction of the corpuscles by the ma- 
larial organism or hemorrhage account for this. Of sepsis and the 
anaemias of infancy I shall speak later. 

IV. Fourth Stage. — The blood of secondary anaemia shows often 
evidence not only of degeneration and destruction of the cells but 
also of regenerative changes. I have already described two regen- 
erative changes — basophilic stippling and diffuse polychromasia; a 
third is the presence of 

^ A heated controversy has spruug up regarding this point and a consider- 
able mass of literature relating to it has accumulated. Without trying to 
present and criticise the evidence I shall content myself with stating that all 
the charges in staining reaction, just described, seem to me best explained as 
evidence of regeneration. ^ 

2 But in the severest forms of anaemia the diameters are apt to be increased. 

6 



82 CLINICAL BLOOD EXAMINATION, 



Nucleated Red Cells. 

These are usually divided into three groups 
(a) Kormablasts. 
(Jj) Megaloblasts. 
(c) jMicroblasts. 

Normoblasts. 

(a) The first are normally present in moderate number in the 
bone marrow of healthy persons, and. in great numbers in the mar- 
row after hemorrhage. They are generally considered to be a 
younger stage in the life of the corpuscle than the non-nucleated 
forms seen in the circulating blood. Hence the appearance in the 
peripheral circulation of this form of nucleated cell is considered to 
mean that, in the comparatively plentiful reproduction of red cells 
called forth in the marrow by tlie ansemia, a certain number of red 
cells leave the nursei-y (the marrow) before they are grown up and 
circulate for a time in their immature state. A normoblast, then, 
represents an immature red corpuscle (see Plate IV. and Plate A. ) 

In size and color it is like an ordinary red cell except that we 
find, usually somewhat to one side of it, a round nucleus about one- 
half the diameter of the whole cell. With Ehrlich's or Wright's 
stain this nucleus stains very deep blue, nearly black, and is sharply 
outlined against the pale yellow of the cell body around it. 

The cell often looks as if it were pushing its nucleus cut, i.e., 
in many instances we see the nucleus projecting over the edge of 
the corpuscle, or half out of it, and occasionally we find it lying 
beside the corpuscle from which it has just emerged; but this ap- 
pearance is probably an artifact and not, as Ehrlich thought, the 
regular way of disposing of the normoblast nucleus. 

Very frequently the nucleus has towards the centre a light spot, 
sometimes so brilliant that it looks like the reflection of light from 
the surface of a drop of ink or any dark liquid, what artists call the 
"high light." Occasionally there are several of these light spots 
in a nucleus, or it may be all light blue-gray except a dark blue 
rim. This is the commonest type of normoblast. But now and 
then we meet with one when the nucleus is more or less separated 
into two or more pieces. These pieces are usually connected by 
pale-staining "bridges," perhaps radiating from a centre so that 



PLATE IV. 

(1) m,m,m,m — Yovng mefj(ilohl<(i<tx. 

(2) D,D,D,D', the tipper two are prohaX>]y old jiormobMsts with degenQvatrng 
tiuclei, and the lower two old megaloblasts with nuclei in a similar condition. 

(3) 0,0,0,0, etc. — The two cells in the lower right-hand corner are probal)ly 
old nmjnlohlasts whose nuclei are nearly absorbed. The three cells immediately 
to the left of these are probably yung tiormobhixt^ — the lowest one being the 
youngest. The other four ceils marked "'0,0,0,0'''' (those to the extreme left) 
are prohnWy at iddle-aged mec/oloblaftts. The two labelled "Xormoljlasts " are 
really old iionnoblaxts. The appearance of extrusion of the nucleus on one of 
them is probably an artifact. The large cell on the extreme upper right-hand 
corner is piol)a])ly a megaloblast with a " pyknotic " or aMlematous (degener- 
ating) nucleus. 

(4) In the young or "typical" megaloblasts {in,m,iii,in) note the white line 
around the nucleus, the variations in its tint, and, in two of them, the discol- 
orations of the protoplasm (polychromatophilia), especially near the nucleus. 
The lower of the two cells in karyokinesis shows the best. 

(5) In the microblast note the ragged edge of the protoplasm. 

(6) In the lower portion of the plate {"" cells deformed in size or sMpe'''') an 
actual field from a case of pernicious anaemia was copied. Macrocytes (or large 
cells), microcytes (or small cells), and misshapen cells or poikilocyteg are shown. 

(7) The '' polycliromatopMlk celW^ in the lower right-hand corner were 
stained with the same mixture as those to the left of them, but have taken up 
other colors besides the orange G, which alone is taken u^) by normal red cells. 



Examlnatjon of the Blood. 



PLATE IV. 



Normal red cells 



6 








Normoblasts 



mm) 



^1 



rSj^ Microblast 



Cells in karyo- 
kinesis 



# 



m 



L 



Varieties of Nucleated Red Cells. 

m. m. m. ra. = Typical uiegaloblasts, D. D. D. D. = Cells with dividing nuclei, 
o. o. 0. 0. 0. o. o. — Other (unQara.ed) varieties of nucleated red corpuscles. 



no 20 



Scale of p. 




4t 




Polychromatophilis cells 



Cells deformed in size or shape. 



R- C. Cabot fee. 



Lith. AnBt. V. E. A. Pimko, Leipzig. 



ANJEMIA AND HYDREMIA. 8d 

the nucleus is "rosette-shaped/^ or it may take any one of a large 
number of different shapes. The parts of the nucleus which are 
nearest the periphery of the cell usually stain more deeply than the 
"bridges'^ which join them. 

Sometimes the nucleus breaks apart completely, and we find 
two or more separate unconnected nuclei within the single cell.' 
Or one of the pieces may be outside the cell and the others inside. 

Barest of all is the appearance of true mitosis in the nucleus of 
a normoblast. 

Megalohlasts. 

(h) The typical megaloblast, as usually described, is so unlike 
the normoblast that we should not naturally think of them as neai.' 
relations. 

It does not occur anywhere in the healthy adult body, not even 
in the bone marrow. In the early foetal marrow and in the mar- 
row and circulating blood of grave forms of anaemia it is to be 
found, usually in company with a certain number of normoblasts. 

The typical megaloblast is an abnormally large cell (11 to 20 ,a 
in diameter), frequently showing abnormal staining (polychromato- 
philia) in its protoplasm, which is, therefore, brownish or purplish 
with the Ehrlich's stain, gray or yellowish with Wright's. Its 
nucleus is very large, filling most of the cell, and contrasts with 
the normoblast nucleus not only by its greater size, but by the 
pale, even stain which it takes up. The commonest color of the 
nucleus with the Ehrlich-Biondi stain is pale green or robin' s-egg 
color; with Wright's stain some shade of blue (see Plates IV 
B, E, andF). 

Cracks and "flaws" are sometimes to be seen in the protoplasm, 
giving evidence, as its purplish stain does, of the necrobiotic changes 
described by Maragliano. 

The outline of the whole may be quite circular : oftener it is 
oval or somewhat irregular, but rarely much deformed. 

Microhlasts 

(c) Microblasts, which are rarer than either of the varieties just 
described, consist of a nucleus like that of a normoblast or smaller, 
and contained in a cell body smaller than the normal red corpuscle. 

*A pparently the nucleus is absorbed or degenerates (see Israel and Pap 
penheim. Virchow's Arcbiv, vol. cxlili.). 



84 CLINICAL BLOOD EXAMINATION. 

Ill the writer's experience the cell body is usually reduced to a few 
shreds of discolored protoplasm changing about the nucleus (see 
Plate IV.). Their clinical significance is generally supposed to be 
that of megaloblasts. 

^^ Atypical Forms.^^ 

We may find in a given specimen of blood only typical normo- 
blasts, microblasts, or megaloblasts, and accordingly can easily 
reckon up the number of each kind and see which type of blood 
formation predominates. But sometimes there are cells present 
about the classification of which we cannot come to a decision, and 
I have occasionally seen a specimen of blood containing a large 
number of nucleated red cells no one of ichich could strictly be 
classed either as a "normoblast," a " megaloblast," or a "micro- 
blast," as these are defined above. The researches of Pappenheim 
have thrown much light on this difficulty. While insisting with 
Ehrlich that the megaloblast and the normoV)last represent respec- 
tively the early foetal and the post-uterine types of blood formation, 
and that there are no real " transitions " from the one to the other, 
he yet recognizes that the two varieties are not absolutely to be 
differentiated by any of the ordinarily accepted criteria such as 
size, color of nucleus, etc. Most "megaloblasts," he admits, are 
larger than most normoblasts, but there are occasional giant normo- 
blasts and dwarf megaloblasts which by size alone are indistinguish- 
able. The large, pale, delicately netted nucleus of the "megalo- 
blasts " is simply a yoiinrj nucleus. All young nuclei are relatively 
large and pale, while the small dark iiucleus of the normoblast is 
simply an old or degenerating nucleus. The real criteria of the 
two varieties, according to Pappenheim, is not the size or color of 
nucleus nor of the whole cell, but the structure of the nuclear net- 
work. This is a point difficult to make out by ordinary staining 
methods and not easily appreciated. Luckily for us, most " megalo- 
blasts " are larger than most " normoblasts " ; and further, most of 
them, as seen in the blood, are young {i.e., have large pale nuclei 
with delicate chromatin network), while most " normoblasts " are 
old, as shown by their small, dark, coarse-skeined nucleus, so that 
in the majority of cases Ehrlich' s criteria for the two varieties are 
sufficiently correct for diagnostic purposes. Pappenheim of course 
wishes to abandon the terms " megaloblast " and " normoblast " 
altogether, but since size still remains the most easily recognized 



PLATE F. 



« 


joff-* 


** . 


f 


»*. 




O 




9i^ 


^ 




« 


f 




4 





Fig. 1.— Erjrthroblasts in Pernicious Ansemia. 
(From a slide kindly loaned by Dr. A. L. Knight, of Cincinnati, and showing an extraordinary 
abundance of erythroblasts.) 




Fig. 3.— Megaloblasts in Pernicious Anasmia. 
(Part of the same slide shown in Fig. 1 above more highly magnified.) 



AX.ICMIA AND HYDREMIA. 85 

criterion of '' niegaloblasts " and " normoblasts " I shall continue to 
use the terms. On the chances, then, aiiy niiclputed red cell over 
10 !>. diavieter sliould he vlassed, as amegcdoblast wliatever the appear- 
ance of its inwleus, and anij nucleated red cell under 10 >>- dlaweter is 
probably a normoblast whatever the appearance of its nucleus. 
Microblasts simply represent degenerating forms (usually normo- 
blasts) whose protoplasm is falling away. [These points will be 
made clearer by reference to Plate IV. and the remarks intended to 
explain it.] 

In most cases of severe secondary anaemia we find a few normo- 
blasts. In very severe forms, whatever the cause, we may or may 
not find an occasional megaloblast. But these are usually rarer 
than the normoblasts, even in the severest types of secondary 
anaemia. The commonest exceptions to this rule are the anaemias 
due to haemolysis, or to intestinal parasites, in which, though sec- 
ondary and curable, the megaloblasts in some cases predominate 
over the normoblasts. 

Summing up the changes characteristic of secondary anaemia, 
which includes almost all the important pathological appearances 
occurring in red cells, we have : 

i (a) Lack of haemoglobin. ) 
L. }(b) Lowered s p e c i fi c :> Characteristic of mild cases. 

/ gravity. ) 

II. The above and necrobiotic / Characteristic of inoderate 
changes of Maragliano. \ cases. 

r (a) Lack of red cells. "l 

TIT ' W P^ssence of riormo- [Characteristic of severe 
j blasts and the above f cases. 

[ (T. and II.). J 

IV. Megaloblasts and the above ] Characteristic of very se- 
(I., II., and III.). [ vere cases. 

The changes in the white cells will be discussed in the next 
chapter. 

Among the commonest causes of secondary anaemia are : I. In- 
fective and febrile diseases, acute or chronic. II. Malignant dis- 
ease. III. Chronic suppurations, nephritis, chronic dysentery, 
cirrhosis of the liver. IV. Bad hygiene, pregnancy, and lactation. 
V. Intestinal parasites. VI. Poisons (lead, arsenic, etc.). 

To discuss the way in wliich each of these influences acts in 
producing anaemia is tempting, but falls outside the plan of this book. 



86 CLINICAL BLOOD EXAMINATION. 

The following are good exaiiii)les of the condition of the blood 

Sec O^ DAK Y ANyEM I A . 



No. 


Age. 


Red cells. 


White 
cells. 


Haemo- 
globin. 


Remarks. 


1 


23 


1,656,000 


2,.300 


18 


Post malarial. 






2,048,000 


2,600 


24 


Seven days* treatment. 






1,808,000 


3,'^HI 


m 


Fouileen days' treatment. 






1,-568,000 


1,300 


.58 


Twenty-four days' treatment. 






4,^48,000 


2,300 


6(1 


Thirtv-four days" treatment. 


2 


22 


1,540,00(1 


2,200 




Malaria an«l dysentery. 


3 


23 


1,984,(K30 


6,700 




.. IW »k 


4 


21 


l,a52,000 


3,:30O 




" 11 n 


.5 


U 


1,248,000 


6,(K>(I 




" 11 Ik 


ti 


23 


l,931,0tK» 


8,600 


Oi") 


.1-:sti\<i-;nitinniiiil malaria. 

Polyiiu.hars. 73: lyraphof-ytes, 24; eosinophiles, 3; 
mefraioblasts = 1 ; nonnoblast.s, i. 


7 


3;-) 


3,070,000 


2,1(K) 


:V} 


Tertian malaria. Boston. 


8 


29 


l,228,f»(K) 


25,l()(j 


9 


Tubal pregnancy, hemorrhage. Polynudeai-s. 92; 

lynipluM-vtes. 7: eosinophiles, 1 ; normoblasts = 6 ; 

me<j;il(.biasts= 2. 
Fibn-id lilceding. Polynudears, 85; lymphocytes, 14; 


9 


51) 


1,960,(M.KJ 


i;;,400 


22 












eosin(>i>liiles, 1. 


10 


64 


1,824,CX)0 


4,800 


25 


Ha-maturia. 


11 


25 


1,448,000 


.3,600 


10 


Portal thrombosis, profuse haeuiatemesis. Polynudears, 
79: lymphoc>-tes, 19; eosinophiles. 2; normoblasts = 

3: mega 1< (blasts — 1. 






906,0(X) 





6 


Ten (lavs later. Death next day. Autt)psv. 


12 


39 


3,200,000 


20.aK) 


.52 


Hepatic cirrhosis. Haemoptysis yesterday! 


13 


46 


2,992,0(H) 


13,800 


20 


Metrorrhagia. 


14 


31 


2,500, ««) 


7,.5(KI 


30 


Chronic diduse nephritis. 


15 


40 


2,040,0! K) 


9,60(J 


10 


Chronic dy.sentery. Polynudears. 6»t.3 : mvelocytes, 1.4 ; 
nonnohiasts = 8 ; megaloblasts = 5. (Four hundred 
cells counted.) 


10 


5:3 


4,a'5(),(K)!i 


]2,7(tl) 


23 


Mitral stenosis. Skin lemon-vellow. Autopsy. Poly- 
nudears. 82; lymphocytes, 18; eosinophiles. 0; me- 
galoblasts = 4 ; normoblasts = 22. (Four hundred 
cells counted.) 


ir 


33 


2,999,00e) 


9,200 


;i') 


Chronic arthritis with ankylosis. 


18 


39 


3,584,000 


12,000 


45 


Alcoholic neuritis. 


19 


30. 


3,496,000 


11,000 


25 


Chronic gastric catarrh. 


20 


42 


3,020,000 


11,600 


5(1 


Tertiary syphilis. 


21 


25 


3,712,0CKJ 


10,200 


411 


Ovarian cyst. 


22 


11 


4,240,000 


11.600 


45 


I-Yiedreich's ataxia. 


23 


9 


4,270,00<J 


9,200 


;i5 


Cervical Pott's. 


24 


58 


2,744,000 


4.000 


60 


Autopsy. No cause found. 


25 


59 


2.444.000 


4.700 


38 


Folynudear, 73 ; lymphocytes, 25 ; eosinophiles, 2 ; nor- 
moblasts = 2 ; megaloblasts = 0. 


26 


43 


1,468,000 


8,700 


12 


Pol>Tiudeai-s. 71 ; lymphocytes, 27.8 ; eosinophiles, 1 ; 
myelocytes, 2 ; normoblasts = 7 : megaloblasts = 1. 
Autopsy, fibroma of jejunum (ulcerative colitis). 


27 


53 


1,472,000 


12,400 


20 


Duodenal ulcer. Polynudears. 75 ; lymphocytes, 23.6 ; 
eosinophiles, 1.2 ; myelocytes, 2 ; normoblasts = 1. 






1,876,000 




19 


Seventh day. 






2,148,000 




17 


Fourteenth day. 






2,440,000 




21 


Twentv-flrst day. 






3,196,000 




23 


Twenty-eighth day. 






2,774,000 


"6,'6(id 


28 
23 


Thirty-tlfth day. 

Forty-thud day. Polynudears, 72.8 ; lymphocytes, 25 ; 
eosinophiles, 2 ; mast cells, 2 ; normoblasts ^ 1. 






2,820,000 




30 


Fiftieth day. 






3,440,000 




43 


Fifty-seventh day. 






3,832,000 




46 


Sixty-fourth day. 






3,885,000 




48 


One hundred and second day. 



2. HyDK.1^3IIA. 

(a) Seen from the opposite point of view almost all cases of 
ansemia are hydraemic. That is, if the total volume of blood is to 
remain approximately constant (as it appears to do), any loss of 



PLATE E, 




Fig. 1.— Ervthroblasts in Pernicious Anaemia. A, Megaloblast; B, "free" nucleus; C, cell 
containing a small remnant of a nucleus which is nearly absorbed ; D, nucleus apparently 
"loose" in a cell. 




Fig. 3.— Myelogenous Leukaemia. A, B, C, Typical myelocytes ; D, E,F, G, and H, cells ia- 
termediiite iR'tween myelocytes and polynuclear neiitrop'hiles ; I, J, cells possessing char- 
acteristics in part of large lymphocytes, in part of myelocytes. 



ANEMIA AND HYDREMIA. 87 

solids (corpuscle substance) must be made up by water taken in 
from the tissues. Hence any anaemic person's blood is thin, watery, 
or hydraemic. Women's blood is somewhat more hydraemic than 
men's, because less rich in cells- Ordinary chlorosis and second- 
ary anaemia show no more water than normal in the serum, but the 
cells are probably somewhat waterlogged. 

(b) In many conditions of dropsy, Avhether from heart or kid- 
ney, we may have more water than normal, both in the plasma and 
in the corpuscles themselves, which are capable of taking up con- 
siderably more than their normal amount of water. 

(c) Any temporary dilution of the blood under the conditions 
mentioned above (ingestion of liquid, lowered blood pressure, etc.), 
is from one point of view a hydraemic condition. 

Xo special clinical significance attaches to it other than that of 
anaemia, whose correlative it is. 

(d) The investigations of Haldane and Smith seem to show that 
the total volume of plasma is greatly increased in certain types of 
anaemia, although its specific gravity remains normal. This is one 
type of hydraemia (see page 6). 



CHAPTER VIII. 

LEUCOCYTOSIS— LYMPHOCYTOSIIS— EOSINOPHILIA— 
ISIYELOCYTES. 

Much confusion has been caused in the past by the failure to 
see in leuksemic blood anything more than an extreme and perma- 
nent form of leucocytosis, while leucocytosis was thought of as a 
mild and temporary leukaemia. 

We know now that they are quite different phenomena, differing 
not in the number, but in the Ibid of cells present in the increased 
numbers. 

Definition. 

There are many difficulties in defining leucocytosis. To my 
mind the term is best used to mean : An increase in the number of 
leucocytes in the ^ferijyheral blood over tlic nmnher normal in the indi- 
vidual case, this increase never involciny o diminution in the jjolij- 
morphonuclear varieties, hut generally a marked absolute and relative 
gain over the number ^ff^eviously present. 

(a) I say " in the peripheral blood " because most observers now 
hold that leucocytosis is not always a real increase in the total num- 
ber of leucocytes in the body, but is often the result of chemotaxis 
or thermotaxis, the cells being drawn or attracted to the peripher}' 
and out of the internal organs. At any rate, in the blood drop 
which we draw (whether also in the internal organs or not), the 
leucocytes are present in increased numbers per cubic millimetre. 
The studies of Muir, Ehrlich, and others have made it clear that 
there are two types of leucocytosis. (1) The first includes onl}' 
leucocytoses of sudden appearance and short duration such as those 
produced by cold baths. Here there is no time for the production of 
new cells and the increase of white corpuscles in the peripheral 
blood corresponds in all probability to a decrease in the nmnber 
ordinarily hoarded in the pulmonary capillaries and elsewhere, the 
total number of leucocytes in the body remaining approximately 
the same. (2) When leucocytosis lasts for months, as is often the 
case in long-standing suppurations and malignant neoplasms, there 



LEUCOCYTOSIS. 89 

is no doubt that leucocytes are formed and turned into the circula- 
tion more rajjidly than under normal conditions. The total num- 
ber of leucocytes in the body is then greatly increased. In such 
cases the marrow is found to be hyperplastic whether the leucocy- 
tosis is due to bacterial toxins (Ribbert) or to long-continued ex- 
perimental injections of albumoses (Taylor). Chronic leucocytosis, 
then, is a function of the marrow. 

(h) In persons not usually to be considered sick, but simply 
somewhat wizened or ill-nourished, the normal count of white cells 
may be as low as three thousand per cubic millimetre. Tor such 
an individual ten thousand cells per cubic millimetre would be a 
decidedly pathological condition. On the^other hand, there are 
persons, usually those of notable vigor and good nutrition, whose 
white cells rarely fall below ten thousand. 

Obviously we must take account of these differences both in our 
definition and in our practice if we are to reason correctly from the 
data of blood examination. 

(c) Further we must lay stress upon the varieties of leucocytes 
whose increase constitutes leucocytosis in distinction from either 
variety of leukgemia (myeloid or lymphatic). 

For instance, given a count of eighty thousand leucocytes per 
cubic millimetre, we cannot tell without knowing the varieties of 
cells present whether the case is a genuine leukaemia or merely a 
leucocytosis symptomatic of pneumonia, suppuration, malignant dis- 
ease, or other conditions. 

(d) Lastly, in order to be sure that the polymorphonuclear cells 
are not decreased, we must know approximately what the normal 
percentage for that individual is. The normal percentage of these 
cells in infancy is from twenty-eight to forty per cent. In adults 
it is much higher, but varies like the total count, according to con- 
ditions of nutrition, etc. Thus the normal for adults is usually set 
at from sixty to seventy per cent, and if we include the obviously 
ill-nourished, but not actually sick, and also those in blooming 
health, we shall have to widen our normal limits considerably. 
From fifty to seventy-five per cent are within normal limits accord- 
ing to the above conception. But obviously we can make no abso- 
lute judgment by a standard so vague. It is much better, I think, 
to consider each individual as his own standard within these limits, 
his count of polymorphonuclear cells being a fair measure of the 
soundness and vigor of his metabolism. Thus, in an obviously 



90 CLINICAL BLOOD EXAMINATION. 

debilitated individual, we should consider seventy-two per cent of 
these cells very higli, while in a vigorous athlete it might not be so. 
In typical leucocytoses of the inflammatory type the percentage of 
polynuclear cells often rises above eighty per cent, swnetimes much 
higher; but very rarely as high as in the case of suppurative men- 
ingitis mentioned l)y Stengel — 99.5 per cent. 

It is the endeavor to include all these limiting conditions that 
has made my definition so long and involved. 

Whether or not differences of race make any difference in the 
normal count of white cells I cannot say, but certainly the average 
of a group of college athletes w^ould be higher than that of some 
country towns in New England, where everybody is more or less 
under-nourished; and if one is to practise among all sorts and con- 
ditions of men, I think he cannot but expect to find people's leuco- 
cytes vary all the way //•»?/? 5,000 to 10,500 per cubic millimetir, 
without there being more tlian malnutrition to jiccount for the lower 
figures. 

We may divide leucocytoses for convenience's sake into: 1. 
Physiological leucocytoses. 2. Pathological leucocytoses. 

Physiological Leucocytoses. 

1. Leucocytosis of the new-born 

2. Leucocytosis of digestion. 

3. Leucocytosis of pregnancy. 

4. Leucocytosis post partum. 

5. Leucocytosis after violent exercise, massage, and cold baths. 

6. Leucocytosis of the moribund state. 

The Leucoci/tosis f>s Affected by Digestion and the Time of Day. 

{a) Total abstinence from food lowers the leucocyte count. In 
the blood of the professional faster Succi, the number sank within 
his first week's fast to 861 per cubic millimetre. After the first 
week it rose to 1,530, and remained there throughout his thirty 
days' abstinence (Luciani).^ The polymorphonuclear cells and eo- 
sinophiles are said by Tauszk to be increased in chronic starvation. 

Von Limbeck counted the blood of a melancholic patient who 
had fasted a week, and found 2,800 white cells per cubic millimetre. 
These facts support the idea that the number of leucocytes depends 
^ "Das Hungeru/' German translation by (?. Frankel. Hamburg, 1890. 



LEUCOCYTOSIS. 



91 



(within certain limits) on the individual's assimilation of food. In 
cancer of the gallet we find similar low figures. 

(b) After a midday meal rich in proteids the leucocyte count 
rises about thirty-three per cent in many sound persons. Ten 
thousand cells may perhaps be considered the average, three to four 
hours after a proteid meal; but if the count before a meal is only 
4,000 or 5,000, digestion will perhaps not raise it above 7,000, 
while vigorous adults may show 13,000. Examples of the midday 
meal leucocytosis in diseases other than gastric are seen in the fol- 
lowing table : 



Case. 


Diagnosis. 


Count before 
food. 


Count after 
food. 


1 


Cirrhosis .... 


10,000 

10,400 

7,500 

5,450 


18,900 

21,700 

13,500 

8,650 


2 


Pneumonia 


3 .- 

4 ... 


Neurasthenia 

Adhesions around gall-bladder. 





Occasionally we see sound persons with little or no leucocytosis 
of this type. 

Any disease of the gastro-intestinal tract, whether functional or 
organic, may prevent the appearance of the midday leucocytosis 
(see later under Diseases of the Stomach, page 436). In anaemic 
and debilitated conditions it is frequently absent. 

Food may call forth a considerable leucocytosis when it is a 
novelty in the stomach. Patients with gastric ulcer who have been 
fed exclusively by rectum for some weeks may show a marked 
leucocytosis after their first meal. 

Japha {Jahrbiich fur Kinderh., IST.F., vol. lii., p. 242), who 
has recently gone over the subject afresh, finds that in infancy there 
is no regular digestion leucocytosis, and that in adults a leucocytosis 
is frequently absent after breakfast and supper, appearing only or 
chiefly after the midday meal, even though the other meals be rich 
in proteids. 

Further, Japha proved that even in fasting persons an increase 
of leucocytes occurs about midday, and hence he believes that the 
so-called digestion leucocytosis represents, in fact, only or chiefly a 
2w/r iodic daily variation like that of blood pressure or respiration. 

Burian and Scliur ^ found an increase of the polymorphonuclear 
varieties in those cases in which an increase of the total count took 
1 Wien. klin. Woch., February 11th, 1807. 



92 



CLINICAL BLOOD EXAMINATION. 



place at all and Japha's figures support this. Eieder reports a 
lymphocytosis. It is probable that both lymphocytes and neutro- 
philes are increased, while eosinophiles are not markedly affected. 

In view of these facts, it seems to me that the so-called diges- 
tion leucocytosis probably represents, as Japha suggests, a periodic 
daily variation — at any rate, in part. In routine blood examina- 
tions allowance should be made for it, but I do not see that it has 
any diagnostic value. 

Leacocytosls of the New-Born. 

The following table is compiled from the best authorities on the 
subject (Schiff, Gundobin, Bayer, Hayem, Carstanjen, Warfield, 
and others) : 



Age. 


Red cells. 


Leucocytes. 


At birth 


5,900.000 
7,000,000 to 8,800,000 
Generally increased, 

6,000,000 
• 5.000.000 


17,000 to 34,000 
24,000 
13,000 


End of first day 


" second day 


" fourth day 




" seven til day. . . 




Tenth day 


10,000 to 14,000 

12,000 

12,000 

7,500 


Twelfth to eighteenth day 

Sixth month 




Sixth year and upward 





The counts just after birth are higher than at any other time of 
normal life. Children born after a long hard labor or delivered 
instrumentally after long labor show the highest counts. 

A fuller discussion of the subject will be found in the chapter 
on the blood in infancy. 

The Leucocytes in Pregnancy 

On the authorit}" of older writers it has been generally stated 
up to the present time in books on the blood (including this one) 
that there is a moderate leucocytosis in primiparae and in fifty per 
cent of multiparse during the later months of pregnancy. But the 
more recent and thorough investigations on this subject have not 
confirmed the earlier statements. 

Greco (A7'chiv. de Ostet. e Glnecol.^ December, 1899) studied 
thirty-six cases and found no leucocytosis and no abnormality in the 
differential count. 

Zangemeister {Deut. med. Woch., July 31st, 1902) compared the 
blood of fifty-seven pregnant women with that of forty-seven 



LEUCOCYTOSIS. 93 

healthy non-pregnant women and found no considerable difference 
between the counts in the two series. 

Ascoli and Esdra (cited from Hahl: Arch, f. GyndkoL, 1902, p. 
491) investigated seventeen cases at various periods in the preg- 
nancy and found no genuine leucocytosis and no progressive increase. 

Hahl {loc. clt.) found practically no increase before the begin- 
ning of labor. 

Leucocytosis After Parturition. 

Hibbard and White (Jour. Exp. Med., November, 1898) studied 
fifty-five cases, thirty-three of which were in primiparse. Twenty- 
four hours before labor eighty-fqur per cent of the primipara? 
showed leucocytosis (i.e., over 10,000 per cubic millimetre), the 
average being 15,000, while in seventy-five per cent of multiparae 
there was some increase (11,700 average). 

After delivery there was a decided fall in the leucocyte count, 
which was normal about the fourth day with a slight secondary 
rise about the fifth to the seventh day post partum. After this the 
leucocytes gradually fell to normal. The leucocytosis was more 
marked in the younger women and in primiparse. 

During labor itself the counts rose from an average of 12,200 to 
an average of 17,600 in primiparse, and from 9,600 to 12,200 in 
multiparse- Mastitis produced a rapid rise of leucocytes. 

In all cases the increase was made up by the polynuclear cells 
alone, while eosinophiles were usually scanty or absent. 

Hahl (loG. cit.) studied thirty-six cases (twenty-one primiparse 
fifteen multiparse) and concludes : " 1. During the last day of preg- 
nancy the leucocytes are somewhat increased. The beginning of 
labor pains produces a further and rapid increase made up wholly 
of the polynuclear cells. 2. In the course of the first week after 
delivery the leucocj^tes return to normal." 

Zangemeister (loc. cit.) confirms the above, and adds that in 
especially difiicult or painful labors the leucocytes are proportionally 
increased (e.g., to 30,000 or more). In the puerperium very high 
counts were found only when there was marked absorption of decom- 
posed lochia. He believes that no diagnostic or prognostic value 
can be placed upon leucocyte counts in the puerperium. 

The articles of Henderson (British Journ. of Ohst. and Gyn., 
1902, p. 168) and of Pray (American Gyn., October, 1902) confirm 
\n essentials these findings. 



94 CLINICAL BLOOD EXAMINATION. 



The Leucocytosis of Violent Exercise. 

Larrabee, Tileston, and Emerson ^ have recently studied the 
blood of eleven men before and after a twenty-five-mile road race 
on foot. Their results are summarized in the table on page y5. 

The most striking point is the resemblance of the blood to that 
found in leucocytoses of the inflammatory or toxic (distinctly path- 
ological) type. Even the abnormal forms of leucocytes — myelocytes, 
transitional neutrophiles, and "stimulation forms " — were present in 
some cases, while eosinophiles were reduced or absent. 

Cold Baths and 3Iassage. 

Thayer studied twenty cases of typhoid and found an average of 
7,724 white cells before and 13,170 after a Brand l)atli (Jo/ins 
Ho2okins Medical Bulletin, April, 1893). The increase took place 
equally in all varieties. Winternitz (Imperio-Eoj^al Medical So- 
ciety, Vienna, Eebruar}^, 1893) came to a similar conclusion and 
found also that prolonged cold bathing decreased the number of 
white cells (dry cold does tlie same). A patient was recently 
brought to the Massachusetts Hospital who had fallen through a 
hole in the ice and been some minutes in the icy water. His tem- 
perature was 91.8^ by the rectum. Blood count showed 17,500 
leucocytes per cubic millimetre. Next day he was perfectly well. 

On the contrar}' , short hot baths decrease and prolonged ones in- 
crease the number of leucocytes. Local warm baths have a similar 
effect, raising the count of leucocytes in the blood of the immersed 
arm if cold and short, and lowering it if hot and short, while pro- 
longed immersion has an opposite effect. In the other arm the 
counts go up when those of the immersed arm go down, and vice 
versa (Eovighi).'^ MitchelP found that the leucocytes showed dis- 
tinct increase (as well as the red cells and liaemoglobin) after one 
hour's general massage. 

These forms of leucocytosis are usualh^ explained by changes in 
blood pressure, and vasomotor changes affecting the calibre of the 
peripheral vessels and consequently their contents. Becker " found 

^ Boston Med. and Surg. Journal, February 19th, 1903. 

2 Arch. Ital. d. Clin. Med., xxxii., 3, 1893. 

3 American Journal of the Medical Sciences. May, 1894. 
4i3eutch. Arch. f. klin. Med., 1901, vol. Ixx. 



LEUCOCYTOSIS. 



95 



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96 CLINICAL BLOOD EXAMINATION. 

that the increase of leucocytes in the capillary blood after short 
cold baths was not maintained in the venous blood. There the 
leucocytes were normal. 

Terminal Leucocytosis. 

The leucocytosis of the moribund state, though by no means 
invariable, occurs in many eases, whether from the influence of a 
terminal infection or from stasis. When death is sudden or rapid, 
it does not occur. It seems to be analogous to the terminal rise of 
temperature seen at the close of many chronic non-febrile affections. 
The longer the patient is moribund the higher the count reaches. 
In pernicious anaemia tlie increase may be so great as to simulate 
lymphatic leukaemia. Such a case occurred in the writer's own 
experience (see also pages 136-137). The patient had presented the 
signs and symptoms of pernicious anaemia. 

Slides taken on the day of death showed a ratio of one white to 
fifteen red cells, the small lymphocytes greatly predominating, but 
the autopsy revealed simply the lesions of pernicious anaemia. Tlie 
differential count of 1,000 leucocytes on the day of death showed : 
Lymphocytes, 91.7 per cent; polymorphonuclear cells, 7.7 per 
cent; eosinophiles, 0.5 per cent. Four megaloblasts were seen while 
counting these. The total leucocyte count was about 60,000. 

In ordinary cases the differential count shows an increase in the 
polymorphonuclear leucocytes. Thus in a case reported by Rieder, 
in which the leucocyte count rose during the last two days of life 
from 7,800 to 59,300, the polymorphonuclear cells constituted 87.5 
per cent of the whole 59,300. 

Pathological Leucocytoses. 

For convenience' sake these may be divided as follows : 

1. Post-hemorrhagic leucocytosis. 

2. Inflammatory leucocytosis. 

3. Toxic leucocytosis. 

4. Leucocytosis in malignant disease. 

5. Leucocytosis due to therapeutic and experimental influences. 

1. Post-hemorrhagic Leucocytosis. 

Within an hour after a large hemorrhage we find commonly a 
considerable increase (16,000-18,000). In hemorrhage from the 
stomach this disappears again, usually within a day or two, while 



LEUCOCYTOSIS. 97 

ill ordinary traumatic liemorrhage it persists longer. This last fact 
may perhaps be explained, as v. Limbeck suggests, by the local 
conditions in the wound rather than by the loss of blood in itself. 

The polymorphonuclear leucocytes are usually increased rela- 
tively and absolutely as in other forms of pathological leiicocytosis. 
Sometimes we have lymphocytosis (see page 118). The average of 
increase in the white cells is parallel in a general way to the anaemia 
produced in the individual, i.e., it depends on his powers of recu- 
peration rather than on the amount of blood lost. Its duration fol- 
lows the same rule.^ 

2. Infiammatori/ Leucocytosis. 

I use the term " inflammatory leucocytosis " rather than " leu- 
cocytosis of infectious diseases " because there is a considerable 
number of infectious diseases in which no leucocytosis occurs, while 
it accompanies almost all forms and cases of inflammation. Never- 
theless I shall class under tliis heading some diseases in which in- 
flammation plays but a very subordinate role. 

I. Although jwrulent and gangrenous processes usually cause a 
higher count of white cells than serous processes, the amount of 
the exudation is not a measure of the amount of leucocytosis. It 
seems to depend rather on the resultant of two forces, viz., the 
severity of the infection and the resisting power of the individual. 
These factors may interact in various ways : 

1. Infection mild : resistance good == small leucocytosis. 

2. Infection less mild : resistance less good = moderate leuco- 
cytosis. 

3. Infection severe : resistance good = very marked leucocy- 
tosis. 

4. Infection severe : resistance poor — no leucocytosis. 

This will be illustrated later under "Pneumonia" and under 
"Sepsis." Experiments on animals show that whereas moderate- 
sized doses of septic cultures, not sufficient to kill the animal, are 
followed by leucocytosis, larger doses, after which death follows 
speedily, do not raise the leucocyte count at all. Animals weak- 
ened by any cause show less leucocytosis to a moderate dose than 
strong animals. 

If the individual reacts from the shock his leucocytes are in- 

* Purtlier account of the blood after liemorrhage will be found on p. 126 

et seq. 

7 



98 CLINICAL BLOOD EXAMINATION. 

creased again and rise above norinal. If reaction fails, the leu- 
cocytes do not rise. 

II. The course of the leucocytosis as regards both amount and 
duration shows, like the temperature chart, certain more or less 
characteristic differences in different cases. 

III. In some diseases, e.g. in measles, in which the absolute 
number of leucocytes is not increased, we see a relative increase in 
the polymorphonuclear cells, pointing to the fact that influences 
are at work similar to those which produce an absolute increase. 

IV. That the amount of exudation is not of itself a measure of 
the amount of leucocytosis is shown by the fact that erysipelas or 
scarlet fever may be accompanied In- as high a count as the average 
count in pneumonia or empyema. 

That purulent exudations usually hav»' more effect on the white 
cells than do serous ones is due, I suppose, to the fact that a puru- 
lent inflammation usually means a severer infection. 

V. Xo direct connection exists between leucocytosis and fever, 
many febrile affections running their course with a normal leu- 
cocyte count. When both leucoc^'tosis and fever are due to tlie 
same causes they rise and fall together, but the correspondence is 
rarely accurate, and marked leucocytosis may exist without fever. 

VI. x\cute, rapidly spreading inflammations seem to produce a 
greater leucocytosis (other things being equal) than those in which 
the process is relatively chronic and stationary. For instance, an 
appendicitis, when well walled off and stationary, shows less in- 
crease in white blood cells than while its lesions are progressing. 
But peracute, overwhelming general sepsis may have no effect on 
the leucocytes, the reactive power of the organism being crushed. 

VII. Most inflammatory leucocytoses are preceded by a tempo- 
rary diminution in the number of leucocytes. This occurs in ani- 
mals from shock of any kind (blows on the head, tying to the ether- 
izing board), and it seems not unlikely that the cause is the same 
in all cases. 

The following is a list of the more important inflammatory or 
infectious conditions in which leucocytosis appears : 

1. Infectious diseases with comparaticely slight local inflamma- 
tory processes : 

(a) Asiatic cholera. 

(h) Relapsing fever. 

(c) Typhus fever (according to the majority of observers). 



LEUCOCYTOSIS. 99 

{d) Scarlet fever. 

(e) Diphtheria and follicular tonsillitis. 

(/) Syphilis (secondary stage). 

{g) Erysipelas. 

(/i) The bubonic plague. 

{I) Yellow fever (some cases). 

2. Infectious diseases with move extensive local lesions : 

(a) Pneumonia. 

(b) Smallpox (suppurative stage) 

(c) Malignant endocarditis, puerperal septicaemia, and all pysemic 
and septicaemic conditions. 

(d) Actinomycosis. 

(e) Trichinosis. 
(/) Glanders. 

(ff) Acute multiple neuritis (febrile stages). 

(A) Acute articular rheumatism. 

(i) Septic meningitis and cerebro-spinal meningitis. 

(j) Cholangitis, cholecystitis, and empyema of the gall bladder. 

(k) Acute pancreatitis. 

(I) Endometritis, cystitis (some acute cases). 

(m) Gonorrhoea. 

3. Local inflammatory processes : 

(a) Abscesses of all kinds and situations, such as : 
Eelon. 

Carbuncle, furunculosis. 

Tonsillar and retropharyngeal abscess. 

Appendicitis, phlebitis (some cases). 

Pyonephrosis, perinephritic abscess, and pyelonephritis. 

Osteomyelitis, empyema. 

Psoas and hip abscess v^hen not simply tuberculous. 

Abscess of lung, liver, spleen, ovary, prostate. 

Salpingitis and pelvic peritonitis, epididymitis. 

(b) Inflammations of the serous 7nembro.neSy including : 
Pericarditis, peritonitis, arthritis (serous or purulent, non-tuber- 
culous), conjunctivitis. 

(c) Gangrenous inflammations, as of the 
Appendix, lung, bowel, mouth (noma). 

(d) Many inflammatory skin diseases, such as dermatitis, pem- 
phigus, pellagra, herpes zoster, prurigo, some cases of universal 
eczema, etc. 

L.oiC. 



100 CLINICAL BLOOD EXAMINATION. 



3. Toxic Leucocytosis. 

XJiider this heading t have grouped most of the conditions not 
obviously to be exphdued as infectious or inflammatory (though 
some may turn out to be such) and not due to malignant disease or 
therapeutic agencies. This classification is chietl}' for convenience' 
sake and represents only a guess at the real explanation of th- 
leoicocytosis : 

{((^ Leucocytosis of illuminating-gas poisoning. 

{!)) '• •• quinine poisoning. 

(>■) " '' ri(*kets (many cases). 

{(I) '• " the uric-acid diathesis, gout. 

(e) " " acute yellow atrophy of the liver. 

(/) " " advanced cirrhosis of the liver (some cases), 

especially with jaundice. 

{(/) " " acute gastro - intestinal disorders (pto- 

mains?). 

(/<) " ''' chronic nephritis, usually in uraemic cases. 

(^) Leucoc3'tosis after injections of tuberculin and thyroid ex- 
tract. 

(y) " after injection of normal salt solution (inti-a- 

venous). 

(A-) " after ingestion of salicylates, potassium chlorate, 

or phenacetin. 

(Z) " during and after prolonged chloroform narcosi- 

(on the effects of narcosis upon the blood 
see page 253). 

Possibly the leucocytosis of acute delirium and some cases of 
acute mania belong also in this group. 

4- Leucocytosis of Malignant Disease, 

Very likely this belongs more properly under one or another of 
the classes just mentioned. Some observers think that it occurs 
only from the inflammation excited in the periphery of some malig- 
nant tumors; others that it is due to absorption of morbid products 
from the tumor itself; others again that it is to be accounted for by 
the cachectic state associated with the growth of the tumors. The 
details and conditions of its occurrence will be discussed later (page 
4-S> 



LEUCOCYTOSIS. lOl 



5. Leucocytosls Due to Therapeutic and Experimental Influences. 

Pohl 1 found that most of the so-called tonics and stomachics 
produce a slight increase in the white cells in animals, particularly 
the vegetable tonics like tincture of gentian and oil of anise seed, 
while bismuth, bicarbonate of soda, and iron had no such effect. 
Quinine, caffeine, and ethyl alcohol gave likewise negative results. 
A^on Limbeck found leucocytosis in men after oil of peppermint and 
oil of anise seed. 

Binz ^ got the same results with camphor. In all these experi- 
ments the substances were given by the mouth. 

Using subcutaneous or intravenous injections, Lowit experi- 
mented on animals with hemialbumose, peptone, pepsin, nueleinic 
acid, nuclein, extract of blood-leech, pyocyanin, tuberculin, curare, 
uric acid, urate of sodium, and urea. All but the last of these pro- 
duce temporary decrease followed by increase of leucocytes. 

Goldschneider and Jacob ^ used extracts of various organs. 
Extract of spleen, marrow, and thymus produced leucocytosis pre- 
ceded, as in Lowit' s experiments, by a brief diminution in the num- 
ber of leucocytes, while extract of pancreas, thyroid, kidney, and 
liver had no effect. 

Winternitz" injected a large variety of substances subcutane- 
ously and found that the degree of leucocytosis was parallel to the 
degree of local reaction excited. 

For example, neutral salts and weak acids or alkalies produced 
slight local inflammation and a leucocytosis of from forty to sev- 
enty-five per cent of the origial count. But irritants like turpen- 
tine, croton oil, nitrate of silver, sulphate of copper, mercury, 
antimony, digitoxin, etc., produced local suppuration (aseptic) and 
much greater leucocytosis (two hundred to three hundred per cent). 

Pilocarpine and antipyrin have been found by von Jaksch and 
others to produce marked increase in the number of leucocytes 
when given subcutaneously. During the use of thyroid extract 
Richter (^Centralhlatt f. inn. Med.^ 1896, p. 3) noted leucocytosis. 
Renzi and Boeri report leucocytosis (slight) after purgatives such 
as castor oil, podophyllin, and scammony. Schreiber {Deut. Arch. 

*Arch. f. exp. Path. u. Pharm.,vol. xv., 1899. 
^Arch. f. exp. Path. u. Pharm., vol. v., p. 122. 
8 Arch. f. Anat. u. Physiol., 1893, p. 567. 
*Arch. f. exp. Path. ii. Pharm., vol. xxxv,, p. 77. 



102 CLINICAL BLOOD EXAMINATKjX. 

/. IJiii. M<'d., 1899, vol. Ixii.; p. 242) found that salicylic acid }»ro- 
duced leucocytosis for the first few da3's of its administration. 

Other drugs which have been reported to produce leucocytosis 
are potassium iodide, spermine, morphine, sodium salicj'late. and 
phenacetin. 

The transfusion of blood of normal salt solution has a like ett'rct 
(see Bibliograjjhy in Da Costa). 

A large number of observations on the effects of injections f)f 
bacteria or their toxins agree in the following results : 

1. When the dose is very large the leucocytes are reduced, and 
the animal dies. 

2. When the dose is iiot sufficient to kill the animal then tem- 
porary diminution in the leucocytes is soon followed by leucocytosis, 

3. When the dose is slowh* fatal the count of leucocytes oscil- 
lates up and down within wide limits. 

.4. Animals previously rendered immune to the poison injected 
show little or no leucocytosis. 

5. Leucocytosis is more easily called forth and of greater extent 
in young animals. 

6. Most pathogenic organisms act similarly, but bacilli and 
toxins of tuberculosis as a rule cause no leucocytosis. 

7. There is no evidence that any one variety of leucocyte is 
attracted by any particular bacillus or toxin. 

In the above sketch of therapeutic and experimental forms of 
leucocytosis no attempt has been made to give anything but the 
more interesting and important outlines of the immense amount r»f 
work done. 

Cell Structure of the Leucocytes in Leucocytosis. 

Hitherto we have spoken as if leucocytosis meant only an in- 
creased number of the normal cells, but one cannot study the cell 
forms in extensive pathological leucocytosis without noting in many 
cases ^-^aZ/fft/u-e changes in the individual cells. These are chiefly: 

1. A greater or less approximation of the nuclei of polymor- 
phonuclear neutrophiles to the appearances of the m^-elocyte nucleus. 
As will be mentioned later under leukaemia, we find in every blood 
containing many myelocj'tes numerous cells whose nucleus is on the 
border line between the myelocyte and the polymorphonuclear 
stage, so far as appearances go. Now in leucocytosis we find the 
same " border-line " cells in smaller numbers, the liTceness to the 



LEUCOCYTOSIS. 



103 



myelocyte sometimes passing into identity in one to three per cent 
of the cells. 

2. Tlirck's '"' Eeizungsformen '^ or "stimulation cells" in which 
the protoplasm of the cell (which is in other respects like a large 
lymphocyte) shows a greater or less approximation to the appear- 




0r%. 



^^^' 




^. 



Fig. 26.— Atypical Leucocytes seen in Leucocytosis. 1, Leucocytes with polar arrangement of 
nuclei (mitosis?); 2 and 3, leucocytes with nuclei resembling those of myelocytes; 4, leu- 
cocyte containing two kinds of granules. 



ance of myelocyte protoplasm, i.e., a diffuse violet or purple color 
exactly as in the myelocyte but non- granular. Engel makes a 
separate variety of this cell, giving it the useless name of " mono- 
nuclear cell." Weil calls it the "non-granular myelocyte." Tlirck 
considers its presence in the circulating blood to indicate a stimula- 
tion of the marrow by the toxins of disease, resulting in the pas- 
sage of this — supposedly immature — cell into the blood. 

3. Other finer changes, such as the number, size, and staining 
power of the neutrophilic granulations, polar position of the nuclei, 
etc. (see Fig. 26), require further study. 

Changes like the above militate against the idea that leucocyto- 
sis is simply a matter of the distribution of fully formed leucocytes 
in the peripheral or internal vessels. 

For an account of iodophilia or the iodine reaction in the poly- 
nuclear leucocytes during suppurations see page pages 42-43. 



104 CLINICAL BLOOD EXAMINATION. 



Ahsenre of Leucocytosis. 

It is of fully as great a practical assistance to us to know that 
in certain infective diseases leucocytosis is regularly absent as to 
know those conditions in which it is to be expected. Among the 
most important diseases in wliich leucocytosis is conspicuously 
absent are : 

(a) Typhoid fever and " paratyphoid " infections. 
(h) Malaria, 
(c) Grippe (most cases). 
{d) Measles, 
(e) Rotheln and mumps. 
(/) Malta fever. 
{g) Cystitis. 

(Ji) Tuberculosis, including — 
Incipient phthisis. 
Miliary tuberculosis. 
Tuberculous peritonitis. 

" ostitis and periostitis. 

" pleurisy. 

" pericarditis.^ 

In some of these affections, notably in miliary tubercle and the 
later weeks of typhoid, the leucocytes are diminished. Further 
details will be given under the special diseases. 

Lp:ucopexia. 

Definition. — A diminution in the number of white cells in the 
peripheral circulation as compared with the number normal for the 
given individual. 

1. The effects of starvation and maluutritiou in producing leu- 
copenia have already been described. Such leucopenia is usually 
associated with lymphocytosis (see below). Cancer of the gullet is 
an example of this class. 

2. Short hot baths or prolonged cold baths produce temporarily 
the same result (Winternitz, loc. cit.). 

3. Most of the infective diseases in which there is no leucocyto- 
sis are sometimes characterized by leucopenia, e.g., grippe, measles, 

* Tuberculous yneningitis often does show leucocytosis (vide infra, p. 303). 



LYMPHOCYTOSIS. 105 

miliary tuberculosis, and other forms of pure tuberculous infection, 
malaria, and especially typhoid, in the later weeks of which it is 
almost invariable, and is accompanied by lymphocytosis. In a case 
of glandular tuberculosis with bronchopneumonia Yaquez and 
Ribierre (Soc. Med. d. Hop., 1900, p. 914) report a great diminu- 
tion both of red cells (to 1,000,000) and of leucocytes (to 2,300) 
the loss involving solely the polynuclears, which were reduced to 
184 per cubic millimetre (eight per cent), while the lymphocytes 
remained nearly normal, 2,116 per cubic millimetre (ninety-two per 
cent). 

P. K. Brown has recently reported a fatal case of infectious 
pharyngitis with intense and continued leucopenia. When a case 
of leukaemia is complicated by an infective disease (pneumonia, sep- 
ticaemia) the number of leucocytes may fall below the normal. In 
a case recently occurring at the Massachusetts General Hospital in 
which a lymphatic leukaemia was terminated by septicaemia from 
glandular suppuration, the white cells fell gradually from 40,000 
three weeks before death to 419 per cubic millimetre on the day of 
death. 1 The differential count was unchanged (lymphocytes = 
ninety-eight per cent). 

4. In pernicious anaemia the count is usually very low and may 
fall below 1,000 cells per cubic millimetre Other severe types of 
anaemia (rachitic, syphilitic, post-hemorrhagic) may produce the 
same result. 

5. Splenic anaemia or the splenic form of Hodgkin's disease is 
often associated with marked leucopenia. 

6. Medicinal leucopenia — following the injection of ergot, tan- 
nic acid, sulphonal, atropine, agaracin, and some other drugs, has 
been described by Bohland {Centralh. f. inn. Med., 1899, vol. xx., 
p. 361). 

Lymphocytosis. 

Lymphocytosis is an absolute and relative increase in the circulat- 
ing lymphocytes. The increase is relative to the number of lym- 
phocytes normal for the individual. When lymphocytosis and an 
increase of the total leucocyte count are present we cannot distin- 

^ Koblank (Dissert., Berhn, 1898) could find \ivX one leucocyte in twent}- 
stained cover-glass preparations from the blood of a case of epilepsy. No 
count was made. In Brown's case (American Medicine, April 19tli, 1902) the 
leucocytes sank to 260 per cubic millimetre before death. 



106 CLINICAL BLOOD EXAMINATION. 

gaish the blood from that of lymphatic leukaemia, and the distiiir-- 
tion must depend upon the course and symptoms of the case. 

1. Such a condition (relative to the adult) occurs in healthy in- 
fants^ hloocl and in many diseases of infancy, the blood seeming to 
have a tendency to return to the infantile type. This is especially 
true of cholera infantum, rickets, and congenital syphilis. Any- 
thing that retards the infant's normal gain in weight or general 
development retards its blood development as well. 

2. Pertussis, as Meunier has recently shown, is accompanied by 
a very marked lymphocytosis, the lymphocytes being quadrupled 
while the polynuclear cells are doubled. The increase is absolute 
as well as relative (see images 107 and 220 j. 

Variola also shows lymphocytosis according to Weil. 

3. Hereditary syphilis is perhaps the best-known cause of rela- 
tive lymphocytosis in children. Scurcy may produce the same 
result. Dividing the anaemias of children into two groups, those 
that do and those that do not produce leucocytosis, it appears that 
the great majority of those whose total leucocyte count is normal 
show a relative lymphocytosis. This is the case irrespective of 
whether there is enlargement of the spleen or not. Sometimes the 
smaller, sometimes the larger lymphocytes are in the majority. 
Often no division between the two kinds is possible. 

4. In adults some forms of debility may be associated with an 
increased percentage of lymphocytes, due in fact to the absolute 
diminution of the neutrophiles. This should be distinguished from 
true lymphocytosis. The same false appearance of lymphocytosis 
may be seen in haemophilia, goitre, cervical adenitis, and other con- 
ditions involving a diminution of the polynuclear neutrophiles, in 
chlorosis, pernicious oMcemia, Graves' disease and the anaemia second- 
ary to syphilis, in the later weeks of typhoid fever and in lactation. 

5. After the administration of thyroid extract, tuberculin, pilo- 
carpine, or quinine hydrochlorate subcutaneously. 

6. The larger forms of lymphocytes are in increased in malaria, 
in some splenic tumors (chronic "ague cake"), and especially in 
the post-febrile stage of measles; also in 'many of the same diseases 
in which the small lymphocytes are increased. 

7. The most marked absolute lymphocytoses known to me (ex- 
cluding leukaemia) occurred in two cases of pertussis-pneumonia m 
infancy. One case occurred at the Massachusetts General Hospital 
in 1894 — in a child of six, who passed through an attack of broncho- 



EOSINOPHILIA. 



107 



pneumonia with uneventful recovery, the only peculiarity of the 
case being the marked increase of white cells running up to 94,600, 
sixty-nine per cent of wliich were lyynphocytes. During convalescence 
the blood became normal and the child left the hospital entirely 
well. In 1900 we had a similar case in a baby of fifteen months, 
well until seized with paroxysms of coughing foiir days before en- 
trance. ^ The spleen and glands were normal. There were no 
hemorrhages and no anaemia. The blood showed 



First day . 
Third day. 
Fifth day . 
Sixth day. 



White cells. 



Per cent 
polynuclear. 



108,000 
104,850 
185,000! 
Death. No 
autopsy. 



35 



Per cent 
lymphocytes. 



64.5 



Per cent, 
eosinophiles. 



0.5 



Remarks. 



Red cells normal. 
No nucleated forms. 



Since reading Meunier's account of the enormous lymphocytosis 
of whooping-cough I have believed these two cases to have been 
atypical whooping-cough. These cases will be referred to later in 
the account of the blood of pneumonia. 

■Diagnostic Value of Lymphocytosis. 

1. I have already suggested that the degree of health in per- 
sons not organically diseased might perhaps prove to vary directly 
with the percentage of polymorphonuclear cells in the blood. 

2. In children the same percentage is to a certain extent a meas- 
ure of the child's degree of development — causes of leucocytosis 
being excluded, and the percentage normal for a child of the pa- 
tient's age being taken as the standard. 

3. Absolute lymphocytosis in the presence of glandular tumors 
is our mainstay in the diagnosis of lymphatic leukaemia, but whoop- 
ing-cough must always be remembered as a source of error. 

EOSINOPHILIA, 

Definition. — An increase in the number of eosinophiles in the 
circulating blood. 



' A similar case has recently been reported by Steven (see page 231). 



108 CLINICAL BLOOD EXAMINATION. 

Phys lolog lea I Kos in nplt II la . 

There is no constant eosinophilia either in infancy or during 
menstruation, as the researches of Carstanjen have shown ; but at 
these periods the number of eosinophiles is subject to remarkable 
oscillation, which 'no doubt has given rise to the impression that 
they are regularly increased. 

Among the causes of j^citholog leal rosinojjlu/ia are: 

1. Bronchial Asthma and Fibrinous Bronchitis. — During parox- 
ysms the eosinophiles are plentiful in the sputum and in the mucous 
membrane of the upper air passages as well as in the blood. In 
the case quoted from Billings (see page 377) there were 53 per 
cent of eosinophiles in a leucocyte count of 8,300. Gabritschewsky 
reports 22.4 per cent in asthma. 

2. Acute and Chronic Shin Diseases. — The most marked cases 
are those reported by Lazarus (60 per cent of eosinophiles in urti- 
caria widely distributed), Zappert (33 per cent, or 4,800 eosino- 
2)hiles per cubic millimetre in penqihifjns). and by Canon (17 per 
cent in prurigo and psoriasis). Ifi dcm/atitis herjjetiformis high 
eosinophile counts are reported by Leredde and Perrin, by Brown, 
and by myself (see page 60o). 

3. Hehninthiasis. — Trichinosis and uncinariasis are the mem- 
bers of this group which have been most thoroughly studied, and in 
both of them eosinophilia is marked and constant (see pages 4VM) 
and 497), but of late evidence is fast gathering to show that filaria- 
sis, Bilharzia disease, hydatid disease, and others, due to animal 
parasites, are likewise associated with eosinophilia. 

Bucklers, working under Leichten stern, has established the in- 
teresting fact that " all varieties of helminthides, from the harmless 
oxyurides to the pernicious ankylostoma, may bring about an in- 
crease of eosinophiles in the blood, often to an enormous extent.'' 
Bucklers reports 16 per cent of eosinophiles in oxyurides, and 19 
per cent in ascarides, and Leichtenstern has quite recently found 72 
per cent of eosinophiles in ankylostomiasis, and 34 per cent in a 
case of taenia mediocanellata (Ehrlich and Lazarus, page 103). 

4. Post-Fehrile. — At the height of most acute infectious fevers 
(except scarlet fever and sometimes rheumatic fever) the eosino- 
philes are greatly diminished or absent. In the post- febrile period, 
however, abnormally high percentages of eosinophiles are often 
found. 



EOSINOPHILIA. 



109 



Tlirck found. 5.67 per cent (430 absolute) after pneumonia; 13.8 
and 9.37 per cent (970 absolute) after rheumatism. Zappert found 
20.34 (1,486 absolute) after malaria; 26.9 per cent (3,220 absolute) 
after tuberculin reaction fever. Grawitz found 90 per cent ( I) 
(41,000 absolute) after tuberculin reaction fever (see page 292). 

5. Malignant Tumors. — Various authors (Weiss, Palma, Rieder) 
have observed a slight eosinophilia in connection with the cachexia 
of malignant disease. It is, however, of moderate degree and sel- 
dom exceeds seven to ten per cent. 

In Eeinbach's study of 40 cases there were 4 with eosinophilia 
as follows: Sarcoma of the forearm, eosinophiles 7.8 per cent; 
sarcoma of the femur, eosinophiles 8.4 per cent; malignant tumor 
of tlie abdomen, eosinophiles 11.6 per cent; lymphosarcoma of 
neck with ulcerative endocarditis and metastases in the bone mar- 
row, eosinophiles 48 per cent (60,000 absolute) (see pj). 457-458). 

Among my cases there is one of generalized sarcoma with eosino- 
philes 12.4 per cent (2,108 absolute). Zappert quotes a case of 
lymphosarcoma with 17,7 per cent (2,077 absolute) and 2 cases of 
cancer (uterus and stomach) with 11 per cent (860 absolute) and 
8.5 per cent (535 absolute). 

6. Compensatory Eosinophilia. — Ehrlich's researches appear to 
show that when the function of the spleen is abolished, either by 
splenectonw or by disease, a late compensatory eosinophilia occurs. 

7. Medicinal Eosinophilia. — After the administration of cam- 
phor, V. Xoorden observed an eosinophilia of 9 per cent in 2 chlo- 
rotic girls. Phosphorus poisoning is also said to cause eosinophilia, 
and Taylor refers to nuclein and pilocarpine as possessed of similar 
properties. 

8. Myelogenous Leukcernia (see page 164). 

•9. Eosinophilia in Hoimatorna, Hemorrha.gic Exudations, and 
Furpura. — Klein (^Centralbl. f. inn. Med., January 28th, 1899) 



Case. 


Date. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Per cent 

poly- 
nuclears. 


Per cent 
eosin- 
ophiles. 


Per cent 
lympho- 
cytes. 


1.., 

2 


March 29 
April 4 
April 11 

(1893) 
April 9 
April 21 

(1894) 


8.800,000 



11,800 
6,200 
8,150 

'9,"l89 


45 


71.7 
56.5 
44. 

^ 69.1 
65.1 


12.5 
37.5 
40. 

6.5 
16.1 


15.8 

6. 

16. 

24.3 

18.7 



110 CLINIC AL BLOOD EXAMINATION. 

reports two cases of lienioi-rhagic pleural exudation with a very 
large number of eosinophiles (74 to 76 per cent) in the exudate and 
a marked increase of circulating eosinophiles : 

Perhaps of a similar type is the eosinophilia exemplified in the 
following report from a case of simple purpura in a girl of eight : 
White cells, 18,000; eosinophiles, 17.5 per cent; polynuclears, 44 
per cent; lymphocytes, 39 per cent. 

10. Eosinophilia in Benign Ovarian Disease^ 

Neusser, in 1892, stated the eosinophiles are increased in dis- 
eases of the female genitals. Kopp (Dissert., Wiirzburg, 1894) 
could find but five out of sixteen cases of ovarian tumors showing 
eosinophilia, but Yoswinkel (Monafschr. f. Gehurtsh. u. Gyndkol., 
1898, p. 413) has carefully studied 126 cases of pelvic disease with 
the following results : 

I. Diseases of the Fallopian tubes, endometritis, and myoma 
uteri (31 cases) show a normal percentage of eosinophiles and no 
myelocytes. 

11. All severe ovarian diseases (excepting in febrile stages and 
excepting also cancer of the ovary) are associated with eosinophilia 
and an increased percentage of polynuclear cells (40 cases). Even 
if the ovary is mostly destroyed eosinophilia is usually present (10 
out of 18 cases). 

III. In cancer of the uterus the eosinophiles may be normal, 
increased, or diminished (19 cases). 

Diminution in Eosinophiles. 

1. During severe muscular exertion. 

2. After castration (jSTeusser). 

3. In febrile stages of pneumonia, grippe, typhoid, diphtheria, 
sepsis, and most infectious diseases accompanied by leucocytosis. 
That this is not due simply to the presence of fever is shown by 
the fact that in malaria and scarlet fever, despite high fever, eosin- 
ophiles may be increased. 

4. In the moribund state eosinophiles are diminished or absent. 

5. Malignant disease, hemorrhage, and most of the other causes 
of leucocytosis also diminish the eosinophiles. 



MYELOCYTES. Ill 



Diagnostic and Prognostic Value of Eosinophilia. 

In trichiniasis eosinophilia is of great diagnostic value. 
Keusser has suggested the following points : ^ 

1. In the diagnosis between puerperal mania and puerperal sep- 
sis, eosinophilia points to the former. 

2. Between a tumor connected with the genital system and one 
not so connected, eosinophilia points to the former. 

3. In determining whether a given case of hysteria, neurosis, 
or psychosis is likely to be benefited by castration, the presence of 
eosinophilia favors the operation. 

4. In malignant disease an eosinophilia points to a metastasis 
in the osseous system (tumors of the spleen are not included in this 
rule). 

5. In cases of doubtful syphilis eosinophilia combined with 
lymphocytosis (see above) speaks in favor of syphilis. 

6. The diagnosis of any obscure form of " uric-acid diathesis " 
is helped by finding an increase of eosinophiles. 

7. In distinguishing malignant liver disease from other liver 
disease eosinophilia points to the latter. 

8. In the prognosis of chlorosis, eosinophilia is favorable. 

9. In the prognosis of scarlet fever and scarlatinal nephritis 
the greater the eosinophilia the better the prognosis. 

10. After hemorrhage increased eosinophiles show active regen- 
eration of blood and good prognosis. 

11. In pernicious anaemia eosinophilia is favorable for the same 
reason. 

MYELOCYTES. 

The occurrence of the myelocyte of Ehrlich in the circulating 
blood is almost always to be looked upon as pathological, that is, 
as the intrusion of a variety of leucocyte naturally a stranger to the 
circulating blood and a permanent inhabitant of the marrow. 
Among hundreds of specimens from healthy persons I have seen 
but one typical myelocyte. 

1. The largest number of circulating myelocytes occurs in 
myelogenous leukaemia (see page 161). 

2. In all conditions" associated with stimulation of the bone 
marrow — that is, in all diseases accompanied by well-marked leu- 

' For none of which I can vouch. 



112 CLINICAL BLOOD EXAMINATION. 

cocytosis or by severe anaemia of any type — myelocytes in small 
numbers may frequently be found. Thus I have found them in 
most cases of pernicious anaemia and of malignant disease with 
leucocytosis. Turck finds them in most acute infections, even in 
typhoid with subnormal leucocyte count. Engel has noted their 
frequent presence in diphtheria, while Neusser ^ has noted them in 
various toxic conditions such as puerperal mania, osteomalacia, 
uraemia, carbonic-acid poisoning, Basedow's disease, diabetic coma. 
Others have recorded their occurrence in rickets, syphilis, phthisis, 
general paralysis, etc. 

The common elements in these various diseases are anaemia and 
leucocytosis. In fact, I do not know of any of the very numerous 
diseases and conditions associated with leucocytosis in which myelo- 
cytes have not been found. Accordingly it seems to me reasonable 
to class them as signifying a marrow stimulation, and as much akin 
to Ttirck's "stimulation forms" (see page 103). 

As a rule I think the j)resence of myelocytes indicates an accel- 
eration of those marrow functions b}" which granular leucocytes 
are furnished to the blood: Such an acceleration ma}^ be supposed 
to take place in leucocytosis, leukaemia, and severe anaemia, which 
are the chief conditions in which mj^elocytes appear in the blood. 

MAST CELLS. 

1. Man}' of the same causes which increase eosinophiles {e.g., 
animal parasites, skin diseases) also increase the mast cells slightly. 

2. A. E. Taylor (Contrib. of Pepper Labor., Phil., 1900, p. 148; 
has noted an increase in one case of carcinoma, one of gonorrhoea, 
one of mycosis fungoides, and two of septic bone disease. 

3. The most constant and extensive increase of mast cells is 
found in myelogenous or mixed-cell leukaemia. 

4. Osier records five to six per cent in a case of ''splenic 
■ anaemia. " In one of mj^ cases they numbered four per cent (632 

per cubic millimetre). 

o. Zollikoffer (Dissert., Berne, 1899) has noted increase of 
mast cells in hysteria, in sciatica, and in articular rheumatism with- 
out fever. jSTo counts are given. 

6. Bigart {La Sem. Med., December 31st, 1902) reports 20.6 per 
cent of mast cells in a case of Hanot's cirrhosis. 

^ Cited in Klein: Volkmaun's "Samml. kiln. Vortrage," December, 1893. 



CHAPTER IX. 

GENERAL PATHOLOGY OF THE BLOOD AS REGARDS HEMO- 
GLOBIN, FIBRIN, LIP^^MIA, MELANEMIA, AND 
HEMORRHAGE. 

H.EMOGLOBIN. 

As stated above, the haemoglobiu may increase and diminish in 
lines parallel to those of the red cells. In that case we suppose the 
amount of haemoglobin per corpuscle to be normal and the color index 
or valeur glohulaire is said to =: 1. When the haemoglobin is dimin- 
ished more than the count of corpuscles, we may say that the color 
index is less than 1. For example, if a man has 5,000,000 red cells 
per cubic millimetre and only 50 per cent of haemoglobin, we esti- 
mate the color index by simply reducing the count of cells to a 
>tated percentage (5,000,000 cells = 100 per cent of cells) and 
dividing this percentage into the haemoglobin percentage — i.e., ^^ 
= 0.5 =r the color index. Therefore 4,000,000 red cells (— 80 per 
cent) with 60 per cent of haemoglobin give a color index of -||- = 
0.075. 

The color index rarely goes above 1, except in pernicious anaemia 
(see below). Here it may be as high as 1.7. As a rule, when the 
red cells are above the normal, the haemoglobin rises equally, some- 
times it lags behind a little, but rarely if ever does it rise higher 
than the cells. 

In most anaemias, as has been pointed out, the haemoglobin 
suffers markedly before any considerable loss of red cells takes 
place. In other words, the corpuscles seem to get thin before they 
die, and except in malaria, hemorrhage, and a few other cases they 
are not destroyed while in the full vigor of health. ^ 

The loss of haemoglobin is loss of albumin, the chief constituent 
of the cells, and hence is usually loss of weight. 

In general the changes in the haemoglobin are best studied in 

' This is of course not literal. There is no reason to suppose that good- 
sized corpuscles get smaller. It is more likely that a smaller generation is 
sent out by the blood-making organs. 



114 CLINICAL BLOOD EXAMINATION. 

connection with changes in the count of red cells, and so far as they 
have not already been mentioned will come in under the various 
special diseases. 

Fjbkix. 

The fibrin network to be seen in normal blood during coagula- 
tion (see page 52) is increased in a considerable number of condi- 
tions. Hayem has studied these minutely, and described several 
varieties of arrangement of filjiin fibres as characteristic of special 
diseases, that is, studied fil)rin (j[ualitatively as well as quantita- 
tively, and also as regards the rapidity of its formation. 

The rate of fibrin formation is often not the same as the rate 
of coagulation. It is not parallel to the number of leucocytes 
or blood plates, at least not in all cases (malignant diseases, 
scurvy). 

In a general way we expect increased fibrin in infectious and in- 
flammatory diseases, but there are notable exceptions to this. The 
greater the exudation and the freer it is (in a cavity or on the sur- 
face) the thicker the filjrin network, while so-called interstitial in- 
flammations or such conditions as parenchymatous nephritis show 
little increase in fibrin. The seat of the lesions lias no consider- 
able influence, except as it modifies the nature of the lesion. An 
abscess in one place has the same effect as an abscess elsewhere, 
provided it is equally free or equally confined, and of the same 
contents. 

Tuberculosis does not increase fibrin if uncomplicated. Leu- 
cocytosis and fibrin behave alike in many respects, especially in 
relation to the vigor of resistance which the individual opposes to a 
given infection. When the individual is so weakened that he dues 
not react well against the infection, the leucocytes and fibrin are 
but slightly increased, whereas in a vigorous individual the same 
infection would have markedly increased both fibrin and leucocytes. 
But neoplasms raise the count of leucocytes without changing the 
amount of fibrin. 

In a general way fibrin increases and decreases as fever does, 
but often persists after fever is gone. 

The most marked fibrin networks are seen in pneumonia, acute 
articular rheumatism, suppurative diseases, and in scurvy. In 
erysipelas it follows the leucocytes (increased in severe, not in mild 
cases). In the early days of grippe it is increased. 



LIP^.MIA. 115 

The fever of hysteria or chlorosis shows no increase of fibrin, 
and post-hemorrhagic ansemia with or without fever shows none. 

Fibrin is diminished in pernicious anaemia, not increased in leu- 
kaemia, typhoid, malaria, malignant disease, non-suppurative dis- 
eases of liver, nephritis (except interstitial nephritis, in which it 
may be increased), heart disease, purpura, haenioglobinnria (some- 
times decreased). 

The most valuable point about the fibrin appears to be the ab- 
sence of any increase in malignant disease whereby a diagnosis 
between the affection and a suppuration may be helped. Otherwise 
the information given by it is chiefly confirmatory of impressions 
given by other features in blood examination. 

LiPyEMTA. 

The blood invariably contains small quantities of fat, especially 
during digestion (v. Jaksch^). 

In the blood of persons suffering from a variety of diseases such 
as phthisis, diabetes mellitus, obesity, alcoholism, nephritis, and in 
some dyspnoeic conditions, suppressed menses, pregnancy, icterus, 
typhus, malaria, mental disease, diseases of the heart and pancreas, 
as well as in health, fat is occasionally to be seen in considerable 
quantities. Grawitz" finds that if the blood is collected in a fine 
capillary tube, and this is kept in a horizontal position for some 
time, fat rises to the surface like cream, and can be seen with an 
oil-immersion lens in the form of fine drops. Gumprecht ^ demon- 
strated it with osmic acid, which stains the fat drops black, and 
proved them to be fat by dissolving them in ether, xylol, etc. 

Lipaemia has no special significance so far as is known, and is 
not characteristic of the diseases above mentioned. Its cause is 
unknown. 

[In almost any preparation of the fresh blood fat drops are to 
be seen unless the patient's skin is washed with alcohol before 
puncturing. Even with these precautions a few drops may often 
be seen in healthy people's blood.] 

' ''Kliii. Diagnostik," p. 75 (Euglish translatiou). 

'^Loc. cit., p. 160. 

3Deut. med. Woch., 1894, No. 39. 



116 CLINICAL BLOOD EXAMINATION. 



]\[ela.v.emia. 

In malaria the occurrence of a black jjigment in the leucocytes 
which have taken plasmodia into themselves is generally to he seen 
during and shortly after a paroxysm. Pigment free in the blood is 
to be seen only at the moment of segmentation among the. new gen- 
eration of parasites. The same condition has been observed in 
relapsing fever and in persons suffering from melanotic malignant 
tumors, the pigment being always in the white corpuscles. Pre- 
sumably it must at some time be free in the plasma, but it is rarely 
if ever seen outside the cells. 

In Addison's disease Tschiikoff > observed })ignient in the leu- 
cocytes. 

Hemokkhagk. 

Women can stand a greater hemorrhage than men. Children, 
on the other hand, succumb to comparatively slight hemorrhages 
(cf. Blood in Infancy, page 510^. Individual differences make a 
great difference in the ability to survive hemorrhage, and no exact 
amount of blood can be stated as the maxinu^m that an}' one can 
lose and yet survive. 

Chatufi'x In thi' Blood ResidtiiK/ from Hfinorrhnfjp. 

The red cells and haemoglobin of course suffer proportionately at 
first; later the haemoglobin in the newly formed cells is always 
deficient (see below). 

The striking point in the blood after hemorrhage is the evidence 
it gives us that even before the hemorrhage has ceased the other 
tissues begin to contribute fluid to make up the volume upon which 
life depends. The serum is markedly diluted by this fluid, l)ut 
still serves to give the heart something to contract on and so pre- 
vents blood pressure from falling as fast as it otherwise would do. 
Were it not for such contributions from neighboring tissues the 
organism could sustain but slight hemorrhage without succumbing 
at once. We have then after hemorrhage a diluted or hydraemic 
blood, even though we do not assist the efforts of nature by con- 
tributing fluid by intravenous or rectal injection. Dock '^ reports a 

'Zeit. f. klin. Med., vol. xix.. 1891. 

-Dock: Trans, of Association of American Flits., 1899, p. 130. 



I 



BLOOD REGENERATION. 



117 



case due to epistaxis in which the count fell to 357.600 per cubic 
millimetre. The counts in this case were as follows: 



Date. 


1 

1 


1 


1 
1 


c 

>-. 

67.3 
69.0 
60.1 

54.0 
57.2 


1 
1 


i 

r 




It 

11 


1 
1 


li 


Remarks. 


Jan. la 

" 16 

" 19 

'^ 20 

" 36 

" 23 

" 25 

" 27 


1,120,000 

357,600 
820,000 

■ 76b',666 

Death 


13,300 
30.500 

49,600 
48,000 


2o% 
20% 


6.2 
2.1 

2.7 

.... 

6.9 
7.9 


21.4 
14.1 

27.2 

25.7 
23.5 


2.6 
3.5 
3.3 

2.3 
1.8 


0.3 

.3 
.4 


0.3 

slo 

9.2 


2.605 
6,900 

22,000 
14,000 


48 megaloblasts 
out of 500 

erytbroblasts. 



All the cover-glass films showed a few red cells in mitosis. 
There is here an absolute increase of all varieties of leucocytes, 
with a high color index and enormous numbers of nucleated red cells. 

Coagulation increases in rapidity the more blood is lost, so that 
after severe hemorrhage it takes place almost instantly. This is 
probably due to the great increase in the blood plates which most 
observers have noted after hemorrhage. 



Blood Regexeratiox. 

The regeneration of the blood after hemorrhage may be taken as 
typical of the same process in anaemia from other causes. 

The length of time needed for full restoration to normal depends 
not merely on the (a) amount of blood lost, but also on the (h) age 
and nutrition of the patient as well as upon (c) the methods of 
^>'mfme^^ carried out and the existence of {d) other disease (typhoid, 
malignant disease, phthisis, etc.). 

Allowing for these other conditions we may say that, other 
things being favorable, the loss of : 

I. Less than 1 per cent of the blood mass is made up in 2 to 5 days. 
IL From 1 to 3 " " " " " " 5 " 14 " 

III. " 3 " 4 " " " " " " 14 " 30 '' 

The last amount means a very severe hemorrhage. Few surgi- 
cal operations involve the loss of over three per cent, and after such 
accordingly we expect the blood to be normal again in two weeks, 
provided the individual is otherwise sound (see Malignant Disease, 



118 CLINICAL BLOOD EXAMINATION. 

page 425). CTiawitz lecoids a gain of 2,000,000 red cells in two 
weeks after a gastric liemorrliage (ulcer). 

Young, well-nourished persons are of course quicker in making 
up losses than the old and weak. 

Blood Condition Duruuj Reycnprofion . 

1. lltd Cells. — (A) As |)reviously mentioned, the haemoglobin 
becomes relatively low as soon as the regenerative process is well 
established, and as i-ecovery progresses the red cells are almost 
always normal in numl)ers for some time before the stature, weight, 
and color of the individual cells is what it should be. A color 
index of 0.50-0.(>0 is not unusual — in short, what some call a 
"chlorotic" condition of \\\v Idood. 

(B) Qualitative cliangesare those already described on page 78, 
namely : (a) Deformation in size and shape with an average diminu- 
tion in size; (/>) polychromatophilic cells; and (/") nucleated cor- 
puscles. These latter arc almost exclusively of the normoblast type, 
but an occasional megalol^last has been observed. 

Blood Crisis. — Von Xoorden was the first to notice that in some 
cases nucleated c(u-})usclcs are to be found in the circulation in great 
numbers for a few hours only, the Idood examination both before and 
after showing fcAV or none at all. Tlie name of ''blood crisis" has 
been given to these sudden outpourings of nucleated red cells; they 
are to be observed duiing recovery from various forms of anaemia. 

2. White Cells. — Immediately after a loss of blood we can usu- 
ally find a decided IcucocytDsis despite the dilution of the blood (see 
above, Post-hemorrhagic Leucocytcjsis). 

This leucocytosis may not differ from those occurring from 
other causes. The percentage of polymorphonuclear cells is usually 
increased, and the eosinophiles often disappear or, as in Dock's 
case, just referred to, all varieties of leucocytes may be increased, 
or, again, as pointed out by Stengel, we may have a lymphocytosis 
after hemorrhage, either from the start or following a polynuclear 
leucocytosis. In his case the percentages were : Polynuclears, 43.5; 
lymphocytes, 43.5; transitionals, 10; eosinophiles, 2.8. A case of 
anaemia from bleeding piles, in which the red cells were 2,723,000 
and the haemoglobin 35 per cent, showed in a total leucocyte count 
of 4,200, 69 per cent of small lymphocytes and only 28 per cent of 
polymorphonuclear cells. Leucocytosis, if present, is rarely very 
high, seldom reaching over 30,000. It is not invariably present, 



CHRONIC HEMORRHAGE. 119 

or, if present, sometimes is of very short duration. Thus in a pa- 
tient whose red cells were reduced to 3,200,000 by a profuse uterine 
hemorrhage the white cells counted next day were only 8,000; 
while in the next bed of the hospital was a woman crushed in a 
railroad accident whose red cells were 1,280,000, and the white 
cells 28,000, the usual state of things. 

The leucocytes may be increased even by a cerebral lieniorrhage 
which is not large enough considerably to affect the red cells in 
most cases. Obviously some other influence is at work in these 
cases (see page 385). 

The effect of transfusion (intravenous saline solution) is appar- 
ently at first to increase the leucocytosis. 

D , a patient with traumatic rupture of the urethra, had had 

severe hemorrhage for forty -eight hours before it was checked at 
1 P.M., November 1st, 1895. At 1 p.m., his pulse being 165, the 
count showed red cells, 3,301,000; white cells, 10,400. He was 
at once given a pint of sterilized normal salt solution by intravenous 
injection under the strictest asepsis. Ten minutes after the trans- 
fusion the leucocytes numbered 32,400. One hour later they were 
24,700, and the red cells 3,632,000. Four hours later, leucocytes, 
31,900; red cells, 3,046,000. The later counts were as follows: 

Red Cells. White Cells. 

November 2d : good pulse 3,608,000 34,600 

3d (5 p.m.): good pulse 2,944,000 30,200 

3d (4 P.M.) : good pulse 2,928,000 15,800 

13th 3,360,000 16,600 

A good recovery was made. 



Chronic Hemorrhage. 

Piles, uterine disease, haemophilia, purpura, and other causes 
may produce a long-standing drain on the blood. 

Some patients apparently can lose a little blood almost daily for 
years without acquiring any severe anaemia, and if the individual 
is otherwise sound and does not suffer from an underlying disease 
like phthisis, cancer, or nephritis, he can probably go on for a long 
time without showing any bad effects from the repeated small hem- 
orrhages. How much he can stand we have no way of judging, for 
we cannot measure the amount of blood lost. When, however, 
such small repeated losses do produce an anaemia, regeneration is 



120 CLINICAL BLOOD EXAMINATION. 

apt to be much slower than after a single large hemorrhage. The 
longer the drain has been going on the poorer the chance for recov- 
ery, and the slower the latter will be if it does take place. 

Gain in body weight does not always mean gain in corpuscle 
substance as well (see Malignant Disease, page 42.">). 



I 



BOOK 11. 



SPECIAL PATHOLOGY OF THE BLOOD. 



PART I. 



CHAPTER I. 

THE PRIMARY ANEMIAS. 
I. THE BLOOD IX PERNICIOUS ANEMIA. 

1. Volume and Oxygen Capacity. — J. Lorrain Smith, studying 
the blood of seven cases by the carbonic-oxide method, concludes 
that ''absolute loss of oxygen capacity (= haemoglobin), which in 
chlorosis practicall}" does not occur, is here of primary importance. 
Whereas, in chlorosis, the oxygen capacity is 95 per cent of the 
normal, here it averages 48 per cent, and in one case was but 28 
per cent." 

The volume of blood is sometimes markedly increased, some- 
times normal, sometimes diminished. Patients with a large volume 
of blood seem to feel worse than those with normal volume, even 
when tlie haemoglobin percentage and count of corpuscles are ap- 
proximately the same. In the remissions of the disease the vol- 
ume may be rapidly reduced. So, for example, 4,305 c.c. with 
1,100,000 red cells per cubic millimetre and later (in remission) 
2,775 c.c. with 3,104,000 red cells per cubic millimetre. 

2. Gross Appearances. 

{a) The drop as it emerges from the puncture is often exces- 
sively pale and watery, but not more so than may occasionally be 
seen in secondary anaemia or chlorosis. Sometimes it is not nearly 
so pale as in other cases with equally low counts, a fact which may 
be due to the increased color index sometimes present (see below). 

In several early cases I have seen the blood as red as normal. 

Another appearance, which I have frequently observed in this 
and other anaemias, is an uneven, streaked color in the drop, as if 
the cells were unequally divided in the plasma. 

(h) As striking as the color of the drop is its great fluidity; the 
rapidity with which it slips off the ear or finger often makes it diffi- 



124 SPECIAL PATHOLOGY OF THE BLOOD. 

cult to suck it up ill time. It is usually very slow in coiigulatiiig. 
Wheu drawn the blood does uot separate into seruiu and clot, even 
after the lapse of seventy-two hours (Lenoble). 

(c) The fresh specimen in most cases shows no rouleaux forma- 
tion, and a marked diminution in blood plates and fibrin. Hayeiii 
says: "This double lesion, rarity of blood plates and loss of retrac- 
tility on the part of the clot, is, according to my latest observations 
(1900), the must characteristic sign of this form of primary ancftmia/" 
I have no experience on this point. 

There are usually great variations in the size and shape of the 
corpuscles with a tendency to an oval shape and an increase in the 
average diameter. Xot infrequently the deformed corpuscle shows 
active pseudo-amoeboid motions of its projecting points or of the 
cell as a whole. The great lack both of red and white cells is no- 
ticeable even in the fresh specimen. 

Red Ct'lh <iiid Hmmoglohm . 

(a) Quantitative changes (see Table I.). The average count of 
red cells in the one hundred and ten cases of my table is about 
1,200,000, which maybe taken as the average count in patients seen 
at the stage of the disease at which they feel sick enougli to seek 
medical advice.' AVe very rarely get an opportunity to examine 
the blood in the early stages of the disease, so that we have to 
judge of them chiefly from the evidence given during the remission 
so commonly observed. In the relapse following such a remission 
the blood count may fall from 5,000,000 to 1,000,000 in a period 
of from six weeks to six months. In the later stages of the disease 
500,000 red cells per cubic millimetre is uot rare, and if the diminu- 
tion has been gradual, the patient may be up and about and able to 
do light work with a count no greater than this. I watched such a 
case in the wards of Dr. F. C. Shattuck at the Massachusetts Gen- 
eral Hospital in 1892, in which for several weeks the blood count 
remained at or near 500,000, yet the patient was outdoors daily, 
read the papers, and seemed perfectly comfortable. Evidently it 
is not the anaemia itself which kills the patient. 

The lowest counts on record are that reported by Quincke— 
143,000 per cubic millimetre, and that of Hills ' — 155,280, 

iCf. Schaumann; Out of his 38 cases, 1 was over 2,000,000; 26 were be- 
tween 1,000,000 and 2,000,000; 11 below 1,000,000, average 1,290,000. 
mills: Boston Medical and Surgical Journal, 1898, vol. 139, p 542 



THE PRIMARY ANEMIAS. 125 

Quincke's case later improved so much that the corpuscles rose to 
1,234,000 within seventy-four days of the count of 143,000. She 
lived several months "fat and well nourished." Hills' case died 
in a few days. 

Table I. 
Pernicious Anaemia (139 cases). 

a. Red cells at the first examination ranged: 

From 500,000 to 1,000,000 in 36 

" 1,000,000 to 1,500,000 in 55 

" 1,500,000,000 to 2,000.000 in 39 

Total cases under 2,000,000 130 

From 2,000,000 to 2,500,000 in 9 

139 

b. Leucocytes numbered (when first examined): 

Under 1,000 11 

1,000 to 3,000 29 

3,000 to 5,000 53 

5,000 to 7,000 28 

7,000 to 10,000 14 

10,000 to 13,000 4 

139 

c. Haemoglobin (first examination) : 

Relatively high in 98 

Not relatively high in 41 

139 

d. Average diameter of red cells at time of final examination: 

Increased in 118 

Not increased in 21 

139 

e. Megaloblasts at time of first examination: 

Predominated in 109 

Later examination, predominated in 27 

Only one examination, no megaloblasts 3 

139 



126 SPECIAL PATHOLOGY OF THE BLOOD. 

/. Lymphocytes avei'ag(3d between 20 por ceut and 30 per cent in. . 41 

' " " •' 30 " " 40 " •' .. 41 

40 •' " 60 •' " .. 47 

60 " •' 80 •' " . 7 

80 " •' 90 •' " .. 3 

139 

g, Eosinophiles averaged : 

Under 4 per cent 116 

Over 4 per cent 15 

None found H 

139 
h. Myelocytes. Present in 86 cases. Highest percentages: 

10 per cent in 2 

9 " " 1 

8 " " 2 

7 " " 2 



The great but temporary improvements above alluded to, fol- 
lowed by relapse, occur either with or without treatment. In the 
course of a few months the count of red cells may rise to normal, 
the nucleated corpuscles (see Cliarts) disappear, and the patient is 
apparently restored to health and goes to work with a laugh at the 
doctor. I have followed, one case through live such relapses in a 
period of three years before the fatal issue came. Frequently the 
patient feels so well during one of these remissions that he goes to 
work and is lost sight of, and, under such conditions, the incautious 
are apt to report "cure." 

The accompanying charts ^ show the three types usually met with; 
No. II. being, of course, only a fragment of a case similar to No. I., 
while the steady progression of No. III. may have been preceded 
by a rise from a former downfall, though no such history was 
obtained. 

Looking over a considerable number of cases, one can hardly 
help being struck with the tendency of the count to remain near 
the figure 1,000,000. The red cells rarely remain stationary at, 
say, 2,000,000, and often death may occur without the red cells 
sinking below 1,000,000. It seems as if some self-applying mech- 

' The number of perpendicular lines represents the number of weeks. 



THE PRIMARY ANEMIAS. 



127 



anism tended to arrest the destruction of corpuscles at or near this 
point. 

In counting the red cells some difficulty and error may result 
from the very small size of some of the cells. It is especially im- 



Haemoglobin V/HAKT i. 

an '.^oOOiX^O 


W kl .. 




70X> ft X. / .. ... "v, .. 


CfW^OMOOO J CZI ^^ '" - >* 


jjj/JOOOW>0 4-i^ \ ^. 


/L j' \ ^ 


50 tX' ^. . - 


tK SDODOnQ \ .. , T_ "' 


^.K.Q000O0 --1 -\ -^r 


w i V V, •' V 


30^ ,t^^ \?r- ^. 






1.0 lIn ■ ■■■ ■ . . 


P' .±- ... -. -. -..--. 



— p— ftedCeMs 
— —— Harmoglobin 

4500000 

^000000 to}, 

dOOOOOO tO/i 

ZOOOOOO 40% 

30% 

■f 000000 kO% 

10% 



CWARTJI 



X 



^tL 



• Red&lls 

HaemojloWrt 

3ODOOOO 60;^ 

ks 00000 sol 
:(oooooo -ffii 

1500000 30t 
1000000 Ml 
500000 101 



Chart HI 



^ 



portant that the diluting solution should be clean and freshly made, 
else without the aid of a stain it may be hard to distinguish the 
dwarf cells or microcytes from bits of extraneous substance. 



Quantitative Changes. 

White Corpuscles (see Table I.). — ^The rule is a very consider- 
able diminution in the number of leucocytes. Thus of 139 cases 
which I have examined 103 were under 5,000, the average of all 
being about 3,800. 

[I have excluded from this series counts made immediately 
after hemorrhage and counts in infants. The latter are very apt to 
show a leucocytosis in connection with any form of anaemia.] 



128 



SPECIAL PATHOLOGY OF THE BLOOD. 



As the disease progresses the leucocytes fall even more rapidly 
than the red cells, and counts as low as 500 white cells per cubic 
millimetre are not uncommon.^ 

Leucocytosis, when present in the blood of adult cases, is always 
due to some complication like hemorrhage or suppuration. 

As mentioned above, the blood plates and fibrin are much 
diminished. 

Table IL — AVhite Cells. — Fikst Examination in Sixty Casks. 



No. 


White cells. 


No. 


White cells. 


No. 


White cells. 


1 


400 
500 
800 
1,000 
1,000 
1,000 
1,500 
1,600 
1.800 
2,000 
2,000 
2,000 
2,000 
2,000 
2,300 
2,600 
2,800 
2.800 
2.800 
2,800 


21 

22 

1 23 

24 

25 

26 

27 

28 

1 29 

30 

31 

32 

33 

34 

35 

36 

37 

38 

39 

40 


2,900 
3,000 
3,000 
3,200 
3,200 
3,300 
3,400 
3,500 
3,600 
3,700 
3,704 
4,000 
4,000 
4,000 
4,Q00 
4,200 
4,300 
4,400 
4,500 
4,720 


41 

42 

43 

44 

45 

46 

47 

48 

49 

50 

51 

52 

53 

54 

55 

56 

57 

58 

59 

60 

Average 


4 828 


2 


4 900 


3 


5 000 


4 


5,200 
5 300 


5 


6 


5,500 


7 


5,600 
6,000 
6.000 
6,000 
6,400 


8 


9 


10. 


11 


12 


6,500 
7,000 
7,200 

7 500 


13 


14 


15 


16 


7,600 
9,000 


17 


18 


9,600 


19 


10 000 


20 


10 100 




= 3.800 + 



In four cases in which Dr. Lindstrom, of Boston, was kind 
enough to give massage, we were unable to see the slightest gain 
either in corpuscles or haemoglobin, such as can be produced tempo- 
rarily in most healthy persons. The observations of J. Mitchell on 
this point Ave were unable to confirm. 

HoRinoglohin. 

The great majorit}^ of cases of pernicious anaemia have a rela- 
tivety high percentage of haemoglobin (e.^., 1,000,000 red cells 
and 35 per cent of haemoglobin, or a color index of 1.75). Ehrlich 
has several times found it over 50 per cent even in the severest 
cases, and once as high as ^h per cent. 

'- Da Costa (page 227) states that in rare instances the leucocytes " appear 
to be entirely absent, none being found after prolonged search through the 
counting chamber and in the stained films " (!?). 



THE PRIMARY ANEMIAS. 129 

This high color index is not, however, peculiar to this disease. 
It has been noted in acute leukaemia, in " splenic anaemia " (McCrae), 
in malaria, in haemolysis from acetanilid, and in leprosy. 

Of the 139 cases in the series on page 125, in which the haemo- 
globin was tested, a color index of over 1 was apparently present in 
98, or 71 per cent, and a color index of less than 1 in 41, or 29 per 
cent, of the cases. How many of these haemoglobin estimations 
may have been wrong I cannot say. 

From the frequency with which we find the corpuscles well 
stained and larger than normal in pernicious anaemia (see below), 
we should expect that the haemoglobin would be relatively high, 
and in a larger percentage of cases than the v. Fleischl instrument 
indicated. 

An increased color index is probably a bad prognostic sign. In 
the remissions of the disease, when the cells are increasing fast, the 
haemoglobin lags behind and the color index is loiu. As the relapse 
follows, the color index in man}^ cases progressively increases. 
Cases whose color index is low and in which the average diameter of 
the red cells is normal are apt to he gaining, at that time, while those 
with high color index are apt to be losing at that time. 

The average color index in the cases in which haemoglobin and 
red cells were both tested was 1.04, the average percentage of 
haemoglobin being 26 and of corpuscles 24 (= 1,200,000). 

Qualitative Changes. 
1. Red Corpuscles. 

We must distinguish here between 

I. The active stages of the disease and 

II. The remissions. 

In the active stages we find : 

{a) Increase in the average diameter of the cells is a very con- 
stant and striking feature of the stained specimens in this disease. 
In no other disease do so large cells or so many of them occur. 

The average diameter may rise as high as 11 to 13 /Jt, but as a 
rule the average is reduced by the presence of a few abnormally 
small forms. The percentage of oversized cells gives us a better 
idea of the facts. Thus Ehrlich in 8 cases of pernicious anaemia 
found the following percentages of oversized red cells : 71, 71, 66, 
65, 60, 58, 57, 56. In 5 convalescent cases 33 to 50 per cent of the 



130 SPECIAL PATHOLOGY OF THE BLOOD. 

cells weve oversized and in the period of complete remission from 
to 14 per cent. 

Out of 139 cases in which I have looked for this point, 109 
showed the increase, as far as could be judged without measuring 
many cells. This does not mean that every cell is larger than nor- 
mal, but that the " macrocytes " are more numerous than the " niicro- 
cytes." Occasionally we see cells over 20 // in diameter, some with 
nuclei, some without.^ 

(b) Defoi^mities in Shajje. — The eye soon gets used to the shapes 
assumed by the necrobiotic corpuscles and learns to distinguish 
them from the distortions due to technique or to crenation. Most 
of them fall under one or another of the types shown in Plate IV. 
The very large forms are generally oval, but seldom present any 
further deformities. Among the smaller cells the battledore and 
sausage-shaped forms are very common. In one case I found all 
the red cells of the latter shape, so that they looked at first siglit 
like a lot of gigantic bacilli. That this appearance was not due to 
the ttechnique ^ (as I had at first supposed) is probable from the fact 
that the rod-shaped cells did not point all in one direction as they 
would have done if pulled out of shape by the process of spreading 
(see Eig. 27c) This appearance is only an exaggeration of what 
may be seen in most severe anaemias, namely, a tendency towards 
an oval shape like that of amphibian corpuscles. This is usually 
true of those cells (in pernicious cases) which are not more violently 
deformed. The type of cell so common in secondary ansemia — well 
stained at the edges and pale in the middle — is rarely seen. 

Occasionally we see cases with no considerable deformities what- 
ever in the red cells. In nine cases out of sixty in which this point 
was observed, little or no deformity was noted. I cannot make out 
that such cases have any better or worse prognosis than others. I 

^ Capps has recently proved the increase in the size of the red cells by de- 
termining in an ingenious way what he calls the volume index. With the 
hsematocrit he determines the volume of the red cells in a given amount of 
blood, and compares this figure with the count. If in a blood containing 
1,000,000 red cells (one-fifth the normal), the column packed down by the 
haematocrit is more than one-fifth as long as that obtained by centrifugaliziiig 
normal blood, then the volume index is above the normal. This high volume 
index he finds regularly in the exacerbations of pernicious anaemia. 

^ Some writers advise the use of less heat than usual in dealing with cover- 
glass specimens of pernicious anaemia. I have not found this so, and heat as 
usual up to 150" C. and then stop. 



THE PRIMARY ANEMIAS. 



131 



have never seen cases whose red cells were all inidersized, but a 
normal average diameter was present in somewhat under one-quar- 
ter of the cases in which I have looked out for this point. 

(c) Staining Properties of the Red Cells. — The white spots or 
streaks described by Maragliano, Hayem, and others are very often 
seen in the red cells of pernicious anaemia despite good technique. 




Fig. 27.— Elongated or Oval Corpuscles in a Case of Pernicious Anaemia. 



Some corpuscles are so pale in the centre that we see only the 
narrow ring of stained protoplasm at the periphery, a mere shell. 
Others are swollen up so as to show no sign of central biconcavity^ 
and stain deeply and evenly all over. 

More common than in any other form of anaemia are the poly- 
chromatophilic red cells (see Plate IV.) which with the Ehrlich- 
Biondi mixture stain brownish, purple, or gray, either as a whole 
or in parts. In cover-slips stained with Wright's stain the spotted 
appearance of the cell, described by Ehrlich and Grawitz, is usually 
marked. In the nucleated red cells the protoplasm is very apt to 
show these changes. With Ehrlich 's stain it may be difficult to 
distinguish normoblasts from lymphocytes. In difficult cases we 
have sometimes to fall back upon the appearances of the periphery. 



132 SPECIAL PATHOLOGY OF THE BLOOD. 

which in most red corpuscles shows some thin place or crinkle char- 
acteristic of a flat cell, while the lymphocyte gives us the more 
solid-looking outline of the splterical cell. With Wright's stain it 
is seldom difficult to make tliis distinction. 

2. Nucleated Red Corjjuscles. 

Nothing further needs to Ije said in descri})tio]i of these forms 
(see pages 82 to 87). W^e have no exact method of estimating 
the number of nucleated cells either in relation to the whole num- 
ber of red cells or in a cubic millimetre. All we can do is to noti- 
the number seen in suclt an area of a cover-glass specimen as is 
covered while counting a given number of white cells, say, 1,000. 
Knowing the ratio of red to white corpuscles, we can calculate from 
this number of nucleated red cells their ai)proximate relation to the 
whole number of red cells. 

■ Thus if the ratio of white to red be 1 : 1,000 (1,000,000 red and 
1^000 white) and we luive seen two nucleated red corpuscles while 
making a differential count of 1,000 white cells, the total number 
of red cells passed over must be approximately 1,000,000 and the 
number of nucleated corpuscles about 2 : 1,000,000 red cells or two 
in a cubic millimetre. Of course when leucocytosis is i)resent and 
the ratio is raised— say, to 1 : 150 (10,000 white and 1,500,000 red) 
finding two nucleated red cells while counting 1,000 white would 
mean that there were two nucleated cells in every 150,000 non- 
nucleated, or twenty in a cubic millimetre (or in 1,500,000 non- 
nucleated cells). 

Such calculations are inaccurate because we are never sure that 
the red cells and white cells are distributed in the dried speci- 
men exactly as they are in the blood. Part of the leucocytes 
may be accumulated at the edges of the cover-glass, so that the 
ratio in the middle may be different from that in the circulating 
blood. 

Nevertheless we can get some idea of how plentiful the nucleated 
corpuscles are, and as their significance in prognosis depends far 
more on their kind than on their number, greater accuracy as to the 
latter is not at present important. For instance, two megaloblasts 
per cubic millimetre mean a worse prognosis than twenty normo- 
blasts, provided there are no other kinds present in either case. It 
is the 7'atio of megaloblasts to normoblasts and not the absolute 
number of each, that is of importance. 



THE PRIMARY ANEMIAS. 133 

In all but three of the cases of pernicious anaeinia in which I 
have examined the blood, the number of megaloblasts has exceeded 
the number of normoblasts, and as the cases grew worse the megalo- 
blasts grew relatively more numerous (often absolutely as well). 
Further, in several hundred cases of severe secondary ansemia I 
have but twice seen the number of megaloblasts exceed the number 
of normoblasts. 

The range of variation in the number of nucleated cells present 
has extended in my series from 6 per cubic millimetre to 7,100 per 
cubic millimetre (see Table III.). The calculation can be made by 
using the following formula : 

Let n = the number of white cells counted (by differential count). 
" m = " " " nucleated red cells seen while counting these. 
" p = " " " white cells per cubic millimetre (Thoma-Zeiss). 
m 
p X — = X = number of nucleated red cells per cubic millimetre. 
n 

The search for nucleated corpuscles in pernicious aneemia is 
sometimes the most laborious undertaking in all blood examination, 
but it is also one of the most important. We may search two or 
three hours before finding one nucleated corpuscle, but on that cor- 
puscle may hang the character of our prognosis. If it be a megalo- 
blast and no other nucleated red corpuscles are seen, the prognosis 
is bad, and it is important that we should know it. This is partic- 
ularly true when the case is seen during a remission, for under 
these conditions we might never suspect a case of pernicious ansemia 
but for the presence of megaloblasts. They are not always difficult 
to find; indeed, in one of my cases they were more numerous than 
the white cells, but, as a rule, we do not get off with less than two 
hours' work. 

The number of megaloblasts in the peripheral circulation often 
varies very markedly from day to day so that to-day it may be im- 
possible to find any, while to-morrow they will be plentiful. Even 
in different preparations made at the same time the number of 
megaloblasts may vary greatly. The importance of frequent exami- 
nations is obvious in the light of these facts. Morse (^Boston Med. 
uMd Surg. Jour., November 27th, 1902) reports a series of cases to 
prove that the diagnosis of pernicious ansemia cannot be made from 
the blood alone, for identical blood occasionally occurs in secondary 
anaemias. 



134 



SPECIAL PATHOLOGY OF THE BLOOD, 



i 


1 


Pi 


a 

1 




i 12 1 ^ 
^'6 ''.It % 

at! 1 cti; a 


1 
I. 


1 

1 


2 
1 


Remarks. 


1 

2 

3 


Malaria 

Bleeding piles 
for 20 years. 

Cancer of 
bladder. 


1,216,000 
diatn. + 
2,208,000 
diam. -\- 
1,280,000 
1,060,000 


9 

35 

8 
10 


4,200 

4,400 

8,000 
7,600 


57 36 i 1 
66 30 3 

48 49 3 


6 

1 



10 

1 

o 

2 


1 


2 




200 counted. 

3(X) counted. 

100 counted. May 1st. 
100 




' 







These cases are, I think, conclusive, and two similar ones have 
within the past few years come to my notice and convinced me that 
by the blood alone the diagnosis of pernicious anaemia is not always 
possible. We must take account of all the clinical data, of which 
the blood is but one. 

Table III. shows the number of nucleated corpuscles per cubic 
millimetre in thirty of the cases examined by the writer. 

Table III.— Number op Nucleated Red Cells per Cubic Millimetre 
IN Thirty Cases op Pernicious Anemia. 



Case Number. 



1 
2 

3 

4 
5 
6 

7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 



Total nucleated 
red cells. 


Megaloblasts. 


Normoblasts. 


Microblasts. 


7,100 


5,300 


1,325 


475 


6,468 


3,476 


924 


2,068 


854 


574 


266 


14 


277 


277 








240 


160 


80 




229 


123 


106 




208 


130 


78 




200 


134 


66 




117 


103 


14 




116 


80 


36 




114 


95 


19 




112 


96 


16 




96 


96 







96 


84 


12 




92 


' 59 


33 




46 


26 


20 




45 


36 


9 




39 


33 


6 




35 


32 


3 




28 


26 


2 




28 


21 


7 




28 


28 







18 


12 


6 




14 


14 







11 


11 







11 


10 


1 




11 


9 


2 




9 


6 


3 




8 


7 


1 




3 


2 


1 





THE PRIMARY ANEMIAS. 



135 



3. White CoT])usdes. 

Unless the cover-glasses are spread unusually thickly, it may 
take a long time to find enough leucocytes for an accurate differen- 
tial count, so great is the leucopenia in many cases. It is worth 
while, therefore, to spread some of the cover-glasses more thickly 
than would be advisable if we had only the red cells to examine. 

Table IV. — Pekcentages of Leucocytes in Pernicious Anemia. 



Lymphocytes, Large and Small. 


EOSINOPHILES. 


Number of 


No. 


Per cent. 


No. 


Per cent. 


counts. 


1 


79. 

77. 

71. 

61.6 

58. 

57.6 

57.2 

57. 

56.9 

56. 

53.9 

53.8 

51.5 

49.5 

49.4 

47.9 

47.9 

47. 

46. 

45.9 

45.5 

44.7 

43.7 

42.2 

41. 

40.8 

40.5 

39. 

38. 

38. 

37.8 

36.1 

35.7 

85.6 

35.6 

34. 

33.6 

33.1 

33. 

33. 


1 


9. 

6.2 

6. 

4.7 
4.6 
4.5 

\X 

4. 
4. 
4. 
3.7 
3.5 
8.4 
3.4 
3.1 
3. 
2.8 
2.7 
3.6 
2.6 
2.6 
3.6 
3. 
3. 
2. 
1.6 
1.6 
1.5 
1.5 
1.5 
1.5 
1.4 
1.2 
1.2 
1.3 
1. 
1. 
1. 
.8 


1 


2 


2 


1 


3 


3 


1 


4 


4 


8 


5 


5 


2 


6 


6 


3 


7 


7 


1 


8 


8 


1 


9 


9 


1 


10 


10 


5 


11 


11 


1 


12 


12 


2 


13 


13 


1 


14 


14 

15 


3 


15 


1 


16 

17 


16 

17 


1 
3 


18 

19 .. 


18 

19 ... 


3 
3 


20 


20 


1 


31 


21 


3 


22 


22 


3 


23 ... . ... 


28 ... 


1 


24 


24 


1 


25 


25 


1 


26 


26 


3 


27 


27 


1 


28 


28 


1 


29 


29 

80 

31 


5 


30 


3 


81 


1 


32 


32 


1 


33 


83 


1 


84 


84 


3 


35 ::.::;:.:. 


35 


1 


36 


36 


1 


37 


37 


1 


38 


88 

89 


2 


39 


1 


40 


40 


1 



136 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table IV. — Percentages of Leucocytes in Pernicious Anemia 

{Continued). 



Lymphocytes, Large and Small. 


EOSINOPHILES. 




Number of 


No. 


Per cent. 


No. Per cent. 


counts. 


41 


31.8 

29.4 

28.7 ! 

28.4 

27.3 

27.2 

26.5 

24.2 

22. 

21.2 

19.8 

16. 


41 


M 1 

8 
7 
6 
5 

3 

2 






1 


42 


42 




43 


43 




44 


44 




45 


45 




46 

47 


46 

47 




48 


48 




49 


49 




50 


50 




51 


51 




52::::::::::::::: 


52 . 











The essential point shown in these tables is the absolute and 
relative diminution in the polynuclear cells which corresponds with 
a percentage increase in the other forms. Absolutely the lympho- 
cytes are about normal. 

In 52 cases examined by myself the lymphocytes (large and 
small) averaged 45.4 per cent. About nine-tenths of these were 
small forms. 1 As the fatal termination approaches, the percentage 
of lymphocytes rises. An extreme case of this change has already 
been recorded on page 96; an ordinary case of pernicious anaemia 
developed near death a lymphocytosis of about 60,000 with 91.7 
per cent of small lymphocytes. 

Williamson and ^Martin " have recently recorded a similar case 
with the following figures : 



Date. 


Red. 


Haemo- 
globin. 


White 
cells. 


Lympho- 
cytes. 


Polymor- 
phonuclears. 


Myelo- 
cytes. 


December 1 


900.000 
480.000 
400,000 
300,000 


20 

12 
12 


34,000 
45,000 
38,000 


99.27 
99.06 
99.62 


0.55 
.56 
.37 




8 

" 11 


0.18 
37 


12 


.00 


Death 





' Da Costa in one-half of his cases foiuid the large forms over 12 per cent. 
The average in all his cases was 10 per cent. The polynuclears averaged 58 
per cent : the eosinophiles were generally decreased and in 18 per cent of the 31 
cases entirely wanting. One case showed 10 per cent, of myelocytes. 

2 Williamson and :Martin : Brit. JNIed. Journal, May 10th, 1902. 



THE PRIMARY ANEMIAS. 



137 



The lymphocytes were of all sizes, but faintly stained. Autopsy 
showed a typical case of pernicious anaemia with terminal pneu- 
monia. Ko signs of leuksemic lesion in marrow or glands. 

Da Costa (page 182) found eighteen hours before death that the 
leucocytes (which had previously numbered from 1,000 to 2,400) 
had risen to 18,600. The lymphocytosis was considerable — 46 per 
cent (or 8,500 absolutely), but not extreme as in the cases above 
cited. Two other cases showed respectively 71 and 79 per cent of 
lymphocytes a few days before death. The polymorphonuclear 
cells suffer proportionately as a rule. On the other hand, Ewing 
has observed a marked rise in the percentage of the polyuuclear 
cells near death, although autopsy revealed no complication. Pneu- 
monia or septic complications may produce an ordinary polynuclear 
leucocytosis. 

Eosinophiles are occasionally increased, 9 per cent being present 
in one of my cases, ^,^ per cent in another. The average of 78 
examinations in my 52 cases is 2.7 per cent. 

Small percentages of m.yelocijtes are the rule. They are present 
in 42 of 52 cases. Table V. shows the percentages. 

Table V. 





Percentage 




Percentapre 




Percentage 




of myelocytes. 




of myelocytes. 




of myelocytes. 


1 


9.2 


19 


1.8 


37 


0.6 


2 


8.8 


20 


1.5 


38 


.6 


3 


8. 


21 


1.5 


39 


.5 


4 


6.3 


22 


1.5 


40 


.4 


5 


6. 


23 


1.4 


41 


.8 


6 


4 6 


24 


1.2 


42 ...... . 


.2 


7 


4. 


25 


1. 


43 


.0 


8 


4. 


36 


1. 


44 


.0 


9 


3.6 


27 


1. 


45 


.0 


10 


3.4 


28 


1. 


46 


.0 


11 


3. 


29 


1. 


47 


.0 


12 


3. 


30 


.8 


48 


.0 


13 


2.7 


31 


.8 


49 


.0 


14 


2.5 


32 


.8 


50 


.0 


15 


2.2 


33 


.6 


51 


.0 


16 


2.2 


34 


.6 


52 


.0 


17 

18 


2.2 

2.0 


35 

36 


.6 
.6 


Average = 


= 2 per cent. 



With a leucopenia such as is usually present in pernicious anaemia, 
2 per cent of myelocytes means absolutely a very small number per 
•ubic millimetre. 



138 SPECIAL PATHOLOGY OF THE BLOOD. 

Taking 3,800 leucocytes per cubic millimetre as the average for 
pernicious anaemia (see page 127), 2 per cent of myelocytes amounts 
to only 76 per cubic millimetre. In leukaemia the absolute number 
of myelocytes is seldom under 150,000 per cubic millimetre. 

In many cases the pol3-nuclear leucocytes show various abnormal- 
ities in size and staining reactions. Tliey are often smaller tliau 
normal, a peculiarity also to be noted in myelogenous leukaemia. 

The Blood in Hemissions. 

1. The Color Index. When the red corpuscles begin to in- 
crease the color index may remain relatively high or even become 
still higher (Laache, Schaumann); Vmt in the majority of cases tliis 
is not so. As a rule, in the remissions of the disease the haemo- 
globin is relatively low, as in ordinary symptomatic anaemia, and I 
have seen two cases which, if examined for the first time during 
the period of remission, would have certainly been mistaken for 
ordinary chlorosis. 

2. The Leucocytes. Coinciding with the increase in the red 
cells there is usually a still greater increase in the leucocytes, so 
that for a time a moderate leucocytosis may be present. This in- 
crease is made uj) very largely of polymorphonuclear neutrophiles, 
and is due, no doubt, to the increased activity of the marrow through 
which both red corpuscles and granular leucocytes are multiplied. 
The eosinophiles may also be increased as in the following case of 
Ehrlich: Eed cells, 4,115,000; white cells, 18,300. Difeerential 
count of 400 colls showed: Polynuclears, 78.2 percent; hmpho- 
cytes, 12 per cent; large mononuclears, 0; eosinophiles, 9.5 per 
cent. In another similar case he found 11 per cent of eosinophiles. 

As the percentage of polymorphonuclear neutrophiles increases 
the percentage of lymphocytes decreases, and the m3-elocytes, 
which are usualh^ present in small percentages during the active 
stages of the disease, disappear. The number of megaloblasts 
steadily decreases, and in their place normoblasts appear for a 
time; later they, too, leave the circulating blood. The size of the 
individual red cells is sometimes greater during a remission of the 
disease than at any other time. In one remarkable case the patient, 
whose symptoms had totall}- disappeared and who was actively at 
work as a newspaper correspondent, dropped in to see me one day, 
apparently in splendid health and spirits. His skin and mucous 
membranes were ruddy red, his haemoglobin 90 per cent, yet to my 



THE PRIMARY AX.EMIAS. 139 

great surprise I found only 2,500,000 red cells to the cubic milli- 
metre. The stained specimens showed the largest red cells which 
I have ever seen, for the most part perfectly well shaped and nat- 
ural looking, but averaging 12 a in diameter. This stage is, how- 
ever, a comparatively short one, and the size of the red corpuscles 
soon becomes normal or subnormal. The abnormal staining reac- 
tions and the oval forms disappear. As a rule, the count of cor- 
puscles does not remain long above 4,000,000, but ranges in the 
neighborhood of 3,000,000 during the greater part of the remission. 

3. The Eed Cells. Usually the proportion of large forms 
diminishes as in Ehrlich's case: («) Active stage; red cells 1,340,- 
000, large forms 66 per cent, (b) Remission; red cells 4,115,000, 
large forms 33 per cent At the beginning of the remission the 
number of megaloblasts diminishes, Avhile the normoblasts increase. 
Later the latter also disappear. Deformities become less marked 
and the achromic cells (pale centres) appear, giving the blood 
the appearance of secondary anaemia. Polychromatophilic and 
spotted cells grow less numerous, but Ehrlich maintains that the 
latter may remain even wdien the blood has otherwise regained its 
normal appearance. He therefore considers '' spotted red cells " of 
value for diagnosis during remissions. 

The rate of regeneration is often astonishingly rapid. 

In Case VII. of my series the red cells increased from 1,800,000 
to 5,200,000 in fourteen days. In Case XXXIX. the red cells 
increased from 2,200,000 to 4,000,000 in thirteen days. In Case 
LVIII. the red cells, increased from 1,500,000 to 3,200,000 in 
twelve days. In Case XCI. the red cells increased from 1,700,000 
to 3,000,000 in fourteen days. 

Similar observations have been reported by Ehrlich and other 
observers. 

It is quite possible, although I have no figures to prove it, that 
in the periods of decline the red corpuscles may fall as rapidly as 
they subsequently rise. This possibility is suggested by the fact 
that one rarely sees pernicious anaemia in an early stage — that is, 
until the red corpuscles have fallen below 2,000,000 per cubic milli- 
metre. Only four of my cases showed more than 2,000,000 red 
corpuscles per cubic millimetre at the time of the first examination 
of the blood. 



140 SPECIAL PATHOLOGY OF THE BLOOD. 

Summary. 

The more important characteristics of the blood of pernicious 
anaemia are as follows : 

1. Red cells about 1,200^000 per ruhk millimetre. 

2. White cells much diminished. 

3. Haemoglobin variable, somMhnes increased relatively (= high 
color index). 

4. Deformities in size and shape of red cells in many cases. 

5. Increase in average diameter of red cells. 

6. Polychromatophilic red cells. 

7. Megalohlasts "inore number ous than normoblasts. 

8. Lymphocytosis. 

9. Small percentage of myelocytes. 

The items italicized are the most important and characteristic. 

Diagnostic Value. 

1. Pernicious ancem^ia and chlorosis may be indistinguishable 
without the examination of the blood. The pallor of the two dis- 
eases is not always different either in degree or in kind, and the 
symptoms and physical signs may be identical. 

The differential diagnosis is easily made by the blood. The red 
cells rarely reach as low as 2,000,000 in chlorosis and the number and 
degree of degenerative changes are less than in pernicious anaemia. 
Megalohlasts have been seen in chlorosis (Hammerschlag), but have 
never constituted a majority of the nucleated red cells present. 
In the great majority of cases the pallor and other signs and symp- 
toms of chlorosis are due to lack of haemoglobin per corpuscle (for 
the corpuscles are not only pale but very small-sized), and not to a 
lack of corpuscles. The high color index and large size of the 
scanty cells in pernicious anaemia contrast strongly with this. 

The white cells are about the same in both diseases, though usu- 
ally fewer in pernicious anaemia. Lymphocytosis is common to 
both diseases. Myelocytes are occasionally found in chlorosis, but 
much less commonly than in pernicious anaemia. 

2. Pernicious Ancemia and the Ancemia oj Jlallgnant Disea.se. — 
Not long ago I examined the blood of a gentleman who had gradu- 
ally and without assignable cause acquired a " lemon-yellow " pal- 
lor, without loss of flesh, vomiting, pain, or any localizing sign or 
symptom. The diagnosis of pernicious anaemia had been made. 



THE PRIMARY AN^.MIAS. 141 

To my great surprise I found over 4,000,000 red cells, with only 
38 per cent of haemoglobin, and 18,780 white cells, 86 per cent of 
which were polymorphonuclear neutrophiles. One normoblast was 
seen. Fibrin was not increased. The anaemia was evidently sec- 
ondary, and the autopsy ten months later showed cancer of the 
stomach. 

Osier and McCrae record a case in which the symptoms and 
signs (except the blood) were so suggestive of pernicious anaemia 
that Osier made that diagnosis. Six months later a nodular mass 
was felt in the region of the stomach, and the patient soon after 
died. In this case the red cells varied between 2,840,000 and 
3,048,000. The leucocytes numbered 11,500 ; there were no nu- 
cleated red cells and but slight poikilocytosis. Haemoglobin was 
25 per cent, i.e., the blood of secondary anaemia. I have since had 
four similar cases. 

Malignant disease may bring down the count of red cells to 
1,000,000 or lower, but in such cases leucocytosis is often present. 
As will be seen in the chapter on malignant disease, leucocytosis is 
by no means invariable in the anaemia of cancerous growth, but in 
those cases which cause such an anaemia as to resemble the counts of 
pernicious anaemia, leucocytosis is the rule. This in itself is usu- 
ally sufficient to exclude uncomplicated pernicious anaemia. When 
an increase in the whole number of leucocytes is not present in ma- 
lignant disease, there is often an increased percentage of polymor- 
phonuclear cells, contrasting strongly with the increased percentage 
of lymphocytes in pernicious anaemia. Nevertheless, it is true that 
the blood of cases of cancer does occasionally simulate for a time 
that of pernicious anaemia so closely that, judging from the blood 
alone, the two diseases are indistinguishable. The other clinical 
data must be kept in mind. 

Normoblasts and not megaloblasts are the rule in malignant 
disease. If megaloblasts are present they are almost always in the 
minority, while in pernicious anaemia they are in the majorit3^ 
The average size and staining power of the red cells is increased in 
most cases of pernicious anaemia and decreased in most cases of 
malignant disease. 

Ehrlich has twice diagnosed pernicious anaemia from the blood 
examination and been confronted at the autopsy with small cancer- 
ous growths in the stomach. In one case the cancer was "the size 
of a hazelnut"; in the other, "an annular fibrous cancer of the 



142 SPECIAL PATHOLOGY OF THE BLOOD 

pylorus without any ulceratiou.'' In these cases I believe the can- 
cer to have been a complication and not the cause of the anaemia. 
Such small growths are very rarely associated with any anaemia 
at all. 

Hayem insists that pernicious anaemia may be distinguished from 
anaemia secondary to cancer, because in cancer the clot contracts 
firmly and squeezes out the serum, and the blood plates are but 
slightly diminished, while in pernicious anaemia the clot does not 
retract and blood plates are greatly decreased. 

3. Pernicious Ancemia and Other Secondary Anaitnias. — Most 
secondary anaemias which are severe enough to reduce the count of 
red cells below 2,000,000 follow the type of malignant disease and 
show leucocytosis. The great pallor and dyspnoea seen in connec- 
tion with some cases of tuberculosis and nephritis rarely mean a low- 
count of red cells, but simply a loss of haemoglobin. I remember 
two cases in adjacent beds at the Massachusetts General Hospital, 
both with extreme yellow pallor without emaciation; one had 
1,020,000 and the other 4,100,000 red cells, the haemoglobin in 
each being about thirty per cent. The first was pernicious anaemia, 
the second nephritis. 

Chronic bleeding from internal piles is sometimes quite unknown 
to the patient, and so leads to an extreme anaemia, which is not 
unfrequently mistaken for pernicious anaemia. Cases of the kind 
have been observed by Ewart {Therap. der Gegeniuart, November, 
1899), by T. K. Brown, and by myself. In details, however, the 
blood is quite unlike that of pernicious anaemia. 

Purpura, typhoid, lead poisoning, chronic malaria, and other 
diseases may reduce the red cells to a point as low as that seen in 
early stages of pernicious anaemia and may not be acconiiKuiied hij 
leucocytosis ; but the absence of changes most characteristic of the 
latter disease (a majority of megaloblasts, increased diameter and 
color index in the red cells) serves in most cases to make the diag- 
nosis clear. 1 Nevertheless, I have been recently convinced that the 
blood of cases of secondary anaemia may exceptionally present ap- 
pearances indistinguishable from that of pernicious anaemia (see 
page 134). Cases involving haemolysis (poisoning by acetanilid, 

1 Another point of difference emphasized by Grawitz is that the plasma of 
pernicious anaemia has a relatively larger amount of solids than that of anae- 
mia secondar}^ to the above diseases. This is hardly a clinically applicable 
test, but is said to be a valuable one. 



THE PRIMARY ANJ5MIAS. 143 

iiitrobenzol, etc.) may also be associated with blood changes like 
tliose of pernicious anaemia, and the bothriocephalus anaemias, which 
show all the blood changes just described, must surely be classed as 
secondary. 

It appears, therefore, that the blood alone is not always sufficient 
for the diagnosis of pernicious anaemia. This is especially true 
during the remissions of the disease, but even in its active stages 
the disease produces changes which are occasionally reproduced in 
all particulars by cases of anaemia whose cause is obvious, especially 
by those involving haemolysis. The blood of pernicious anaemia 
appears to be the result of one type of chronic haemolj^sis. 

4. Fernicious Ancemia and Leukmmia. — Occasionally in infants 
these two diseases seem to approach very near each other and are 
difficult to distinguish. In infancy, as is well known, any anaemia 
(primary or secondary) is apt to be accompanied by leucocytosis and 
an enlarged spleen. Further, leukaemia, which in adults usually 
causes a relatively slight anaemia, affects the red cells much more 
strongly in infancy, and may reduce them to a number decidedly 
suggestive of pernicious anaemia. Therefore in both diseases we 
may have enlarged spleen, great anaemia, and leucocytosis. 

The one characteristic point of leukaemic blood — the abundance 
of myelocytes — usually enables us to distinguish the two diseases, 
for although present in both diseases the myelocyte is much more 
plentiful in leukaemia. Unfortunately we have no way of fixing 
just lioiv numerous myelocytes must . be in order to constitute leu- 
kaemia. It is only in infancy, and very rarely then, that this diffi- 
culty arises, but at that period I am inclined to believe that we 
sometimes see conditions intermediate between the two diseases, 
indicating the ultimate identity of the two. Their numerous clini- 
cal resemblances cannot here be discussed. (For further comment 
on this point see page 525.) 

Peogxostic Value of Blood in Pernicious Anemia. 

The prognosis is always very bad, but the following scheme in- 
dicates the presence of a severe or of a mild type : 

1. Severe {rapidly fatal). 2. Less Severe {slower course), 

{a) Extreme progressive an- («) Kemissions. 

aemia. 

{h) High color index. (J)) Normal or low color index. 



144 



SPECIAL PATHOLOGY OF THE BLOOD. 



(c) luciease in size of red cells. 
{d) Degenerative changes, 
(e) Numerous megaloblasts. 
(/) Few or no normoblasts. 
(^) Lymphocytosis. 



(c) Normal-sized or small cells. 
(rZ) No degenerative change, 
(e) Numerous normoblasts. 
(/) Few megaloblasts. 
{g) Normal percentage of poly- 
morphonuclear cells. 

It has been thought by some observers that the absence or great 
scantiness of nucleated corpuscles indicated lack of any effort at 



• ••• • *J ••«• • • • 



Fig. 28.— Normal Blood. Magnified 350 diameters. 

regeneration on the part of the blood-making functions, and hence a 
peculiarly malignant type of the disease. I have never seen cases 



Pernicious anaemia. 

About i.O^.CKX) 

Usually decreased 

Often relatively higli. . . 
Constitute the majority 

of the nucleated red 

cells. 
Less numerous than the 

megaloblasts. 

Increased 

Increased 

Decreased 

Common 



Chlorosis. 

Rarely under 2,000,000 

Usually normal 

Always relatively low 

Rare 

Occasional ; always more 
numerous than megalo- 
blasts. 

Diminished 

Increased 

Decreased 

Rare 



Secondary anaemia. 



Red cells 

White cells. . . 
Hteuioglobin . 
Megaloblasts 



Normoblasts. . , 



Size of red ceUs 
Lymphocytes... 
Polymorphonu - 

clear cells. 
Myelocytes 



May be 1,000,000 or less. 
Usually increased. 
Relatively low. 
Rare : never more numer- 
ous than normoblasts. 

Common. 



Various ; not increased. 
Usually diminished. 
Usually increased. 



Rare. 



THE PRIMARY ANiEMIAS. 



145 




Fig. 29.— Pernicious Angemia. Magnified aju diameters. Note tbe relatively large size and 
well-stained centres of the cells. 



^ 




Fig. 30.— Chlorosis. Maffnilied 350 diameters. Note small size and pale centres. 

10 



14(5 SPECIAL PATHOLOGY OF THE BLOOD. 

in which nucleated corpuscles were steadily absent, but their scanti- 
ness has seemed to me as a rule to be associated with a more filoirly 
fatal type of the disease . 

No significance has seemed to me to attach t(j the presence ot 
larger ^r smaller percentages of eosinophiles. 

To illustrate the different size of the cells in chlorosis and per- 
nicious anpemia I have had photographs taken of the blood of a case 
of two of these diseases and of normal blood, all on precisely the 
same scale (see Figs. 28, 29, oO). 

2. FATAL AN.EML\ WITH HYPOPLASTIC MARROW. 
( ' ' Aphist ic Ancem ia . " ) 

Ehrlich reported in 1888 ^ tlie case of a girl of twenty-one with 
cutaneous, uterine, buccal, and retinal hemorrhages, which caused 
death within thirty days from the first symptom. Blood examina- 
tion showed 213,360 red cells — small, fairly stained forms predomi- 
nating. Deformities were sliglit. Xo nucleated red cells could be 
found despite many hours' search before and after death. Leuco- 
cytes numbered 200 per cubic millimetre — an astonishing leucopenia. 
Eighty per cent of these white cells were lymphocytes and 6 per 
cent large mononuclears, leaving ])ut 14 per cent (or 28 per cubic 
millimetre) of polynuclear neutrophilic cells. In other words, the 
neutrophiles were reduced to about ^ f^ of their normal number, 
while the lymphocytes were distinctly though less markedly dimin- 
ished. Eosinophiles Avere Avanting altogether. 

The great diminution in red cells and granular leucocytes in this 
case suggested to Ehrlich a lack of compensatory reaction on the 
part of the marrow. Autopsy confirmed this. The marrow of the 
femur was yellow throughout except for a tinge of red near one end. 

Similar cases have lately been reported by Lipowski,- Muir,' 
and others. In these, as in Ehrlich's case, hemorrhages were 
prominent. 

The red cells in Muir's case were normal in size and their num- 
ber was reduced to 800,000 and the haemoglobin to 11 per cent. 
The leucocytes numbered 7,000 per cubic millimetre, but only 25 
per cent of them were polynuclear neutrophiles. Eosinophiles and 
blood plates were entirely absent. No nucleated red cells could be 

' Charite-Annalen, xiii. -Lipowski: Deut. med. Woch., 1900, p. 340. 

^Miiir: Brit. Med. Jour., 1900, p. 910. 



THE PRIMARY ANJ^.MIAS. 147 

foimd in the blood, and only one or two in the marrow, post mor- 
tem, despite long and earefnl search. The marrow was of the fatty 
type, almost white, and contained few neutrophiles and no eosino- 
jjh lies. 

In Lipowski's case, as in Ehrlich's and in Mnir's, the disease 
was dubbed " purpura hsemorrhagica " owing to the profuse hemor- 
rhages from mucous, serous, and cutaneous surfaces. The red 
cells were 2,112,000, haemoglobin was 18 per cent. Only 7 per 
cent of the leucocytes were neutrophiles, the rest lymphocytes. 
Nucleated red cells were absent. 

3. THE BLOOD IN CHLOROSIS. 

This has been already described for the most part under the 
heading of Secondary Anaemia. In many cases the two are indis- 
tinguishable by the blood examination alone, the changes consisting 
simply in the presence of light, small-sized, pale, more or less de- 
formed red cells whose number may or may not be decreased, accord- 
ing to the severity of the case. Leucocytosis is rarely if ever pres- 
ent in uncomplicated chlorosis, \mt is often absent in secondary 
ansemia. Normoblasts may be present in botli. The chief points 
of distinction are : 

(a) Tlie red cells are more apt to be uniformly under-sized- and 
under-colored in chlorosis, while in secondary anaemia we more 
often find normal cells among the diseased ones, 

(h) The color index may be lower in chlorosis than is common 
in secondary anaemia, and this lowering is more constant in chlorosis. 

(c) Absolute diminution in the number of polynuclear leucocytes, 
which is very common in chlorosis, is not so common in secondary 
anaemia. 

(d) Nucleated corpuscles are less common in chlorosis than in 
anaemia secondary to malignant disease. 

(e) Coagulation is rapid, in contrast with the very slow clotting 
of pernicious anaemia and of many secondary anaemias. Yet fibrin 
is not increased. The increased rate of coagulation seems to be 
connected with the marked increase in blood plates, which is 
almost always present. 



148 SPECIAL PATHOLOGY OF THE BLOOD. 

Volume and Oxi/gen Capac'itij of the BJood. 

The blood volume is greatly increased. In 21 cases with haemo- 
globin below 50 per cent Smith found the average volume 4,883 
C.C., or over one-half greater than the normal average (3,-40). 
The volume is increased in proportion to the severity of the disease. 
Some cases showed 6,400 c.c. of blood, or nearly double the aver- 
age. At the same time the total oxygen capacity (or total haemo- 
globin) is approximately normal, averaging over 95 x^^r cent in '11 
cases. As the specific gravity of the plasma is normal, there iip- 
pears to be a great increase in the amount of normal plasma. If 
we were to imagine this excess of plasma filtered off, there would 
remain {e.g., in Case X. of Smith's series with 6,266 c.c. and 
2,600,000 red cells) about 8,000,000 red cells per cubic millimetre. 
Hence Smith concludes that there is really a large absolute increase 
in the number of red and white cells disguised by an excess of 
plasma. Under treatment the oxygen capacity or haemoglobin is 
not really increased, but the amount of plasma diminishes — in one 
case from 4,574 c.c. to 2,800 c.c. 

The Blood in Gross. 
The pallor of the drop is sometimes excessive, fully as great as 
in pernicious anaemia; the liquid is very fluid and thin, and flows 
abundantly on puncturing the skin. Yet it coagulates very rapidly 
and our technique must be proiiqit. 

Red Cells axd H-EMOCtLobtx. 
Quantitaflrr ( lia ngcs. 

Ha3'em has recorded cases whose count was as low as 1,662,000 
and even 937,360 per cubic millimetre. Such figures are certainly 
rare in this country, and the striking fact is usually the slight 
numerical loss of red cells, considering the extreme pallor of tlie 
patients. 

The lowest count in the Massachusetts General Hospital series 
was 1,932,000, in AT. S. Thayer's 63 cases 1,953,000, and in Ba 
Costa's 1,720,000. The accompanying tables, from the records, 
show the range of red cells and haemoglobin in 192 cases as counted 
when the patients first came under observation. The highest counts 
(7,100,000 and 5,884,000) are undoubtedly due to some temporary 
stasis or concentration of the blood. 



THE PRIMARY AX.^3IIAS. 149 

The average of the 192 cases, 4,052,000 red cells per cubic milli- 
metre, is about the same as in Thayer's ^ series, the average of which 
is 4,096,544, while Da Costa's average in 106 cases is 3,876,000. 

The average haemoglobin percentage of this series, 40.4 per cent, 
is also very close to Thayer's (42.3 per cent) and to Da Costa's 
(41.3 per cent). This gives us a reduction of the corpuscle sub- 
stance to one-half the normal, or to the equivalent of 2,250,000 
healthy red cells; 101 of the 192 cases have 4,000,000 or more red 
cells. These figures do not agree with those collected by v. Lim= 
beck, in which only 99 out of 247 are over 4,000,000. But this 
probably means simply that in this country the patients seek medi- 
cal advice before their disease has advanced very far, w^hile in Ger- 
many they wait longer before resorting to a hospital. For, as above 
explained, in all anaemias the individual corpuscles suffer in qual- 
ity first and only after some time begin to decline in number. This 
is especially the case in chlorosis, although by no means peculiar 
to that disease. 

The color index is invariably low, as seen in the table, although 
it is rare to see it fall below 0.30. In only four cases of the present 
series did it go below that figure, the average being about 0.50. 

V. Xoorden '■ found that the color index was especially apt to 
be low in first attacks and less often in the recurrent or habitual 
cases, but Romberg,^ in a study of one hundred and seventeen cases, 
has not found this true, and I agree with Romberg. One of the 
lowest color indexes in my series was in a woman over fifty who 
had a truly habitual chlorosis. 

Table VI.t-Chlorosis. 

Red Cells. Cases 

Between 7,000,000 and 8,000.000 1 

6,000,000 •' 7,000,000 2 

5,000,000 " 6,000,000 26 

4,000,000 " 5.000,000 72 

3,000,000 ■' 4,000,000 64 

2,000,000 " 3,000,000 26 

1,000,000 " 2,000.000 1 

Average of these 192 cases = 4,052,000 

' See Osier's article on Chlorosis in the " American Text-Book of Medicine, " 
vol. ii., 1894. 

•-"Chlorosis," Wien, 1897 (Holder). 
"Berl. klin. Woch., June 28th, 1897. 



150 



SPECIAL PATHOLOGY OF THE BLOOD. 



White celh 




Cases 


26,000 




... 1 


Between 15,000 


and 14,000... 


... 4 


14,000 


" 13,000... 


... 3 


13,000 


" 12,000... 


... 9 


12,000 


" 11,000... 


...13 


11,000 


" 10,000... 


... 15 


10,000 


'^ 9,000... 


.. 12 


9,000 


" 8,000... 


...10 


8,000 


" 7,000... 


.. 34 



I White ceils. Cases. 
Between 7,000 and 6,000 30 



6,000 
5,000 
4,000 
3.000 
2,000 



5,000 20 

4,000 17 

3.000 10 

2,000 2 

1,000 2 



182 



Average, 7,810 



PkU CkNT of II.KMOfil.OTUX IN ClII.OKOSIS. 

Between 10 and 19 = 9 cases. 

20 " 29 = 36 " 

30 '■ 39 = 53 " 

40 " 49 = 40 " 

50 " 59 = 41 •' 

60 " 69 = 1(5 •' 

70 " 80 = 3 •' 



197 •' 
Aveiasre. 40.4 per cent. 

The striking contrast is with pernicions anaemia, rather than 
with secondary aneeniia. In the former the color index, as above 
mentioned, averaged 1.04 in 68 cases. In secondary- anaemia it is 
almost always below 1, bnt does not accraye so low as in chlorosis, 
although in individual cases it may be very low. 

For example, Osterspey quotes a case of gastric cancer with a 
blood count of 4,2o0,000 red cells, and only 22 per cent of hcemo- 
globin, a color index uf 0.20. 

Qudlifntifo Chanf/cs. 

(^a) The stained specimen shows a greater or less degree of ^nd- 
lor of the coqnisde centirs corresponding so accurateh' to the dimi- 
nution in haemoglobin that a practised observer can tell approxi- 
mateh' ho^v low it is simply from the stained specimen. The 
pallor, however, is to be taken in connection with the slzr of the 
cells, for the dinnnution in haemoglobin is not due simply to a 
bleaching out of the cells, but to their loss of size. Hence, 

(/>) The diminution in the a cerate diameter of the cells is a very 
important feature. In the convalescent we may watch the gradual 
increase in the average diameter of the cells from 5.5 ,a or lower up 



THE PRIMARY ANAEMIAS. 151 

to 7.9 // or even 8.2 ,a in many cases. Both in this respect and 
as regards the bleaching of individual cells, many cases contrast 
with most secondary anaemias, in that a large proportion of the 
cells are affected alike, i.e.^ are small and pale, while in secondary 
anaemia there are apt to be well-stained and good-sized or over-sized 
cells in ever}' field. These last occur also in chlorosis, but less fre- 
quently as a rule. Hence the usually lower color index of chlorosis. 
In certain cases this distinction does not hold, and the two condi- 
tions are identical in so far as the size and color of the red cells are 
concerned. 

(c) Deformities in size and shape are very common in all ad- 
vanced cases, but often absent in mild or moderate ones. They 
present no special peculiarities except that macrocytes are relatively 
rare and microcytes relatively common. In the severest cases, 
however, the macrocytes begin to get more numerous and we ap- 
proach the picture of pernicious anaemia. 

{d) Changes in Staining Reaction. — Polychromatophilia, baso- 
philic red cells, or stippling is rare, but, despite Grawitz's state- 
ment, may be occasionally seen in severe cases. 

(e) Nucleated red corpuscles are very scanty even in advanced 
cases. Most observers find them in small numbers after long 
search. They are almost always of the normoblast type, but megalo- 
blasts have also been found. In four cases of my series normoblasts 
in small numbers have been found — never more than one hundred 
and twelve per cubic millimetre. I have never found megaloblasts. 

The scantiness of nucleated red cells is a point of contrast with 
the anaemia secondary to malignant disease, in which even in mildly 
anaemic states we readily find nucleated corpuscles, while in chloro- 
sis, even in severe cases, a long search may show very few or even 
none at all. 

Specific Gravity. 

Chlorosis is usually agreed to be one of the diseases in which 
specific gravity and haemoglobin run parallel, and as the inaccuracies 
and inconveniences of the v. Fleischl instrument are so great, it 
seems to the writer better to follow the specific gravity rather than 
the liaemoglobin. The tables on page 39 (Part I.) show how the 
in:?3rence from density to coloring matter can be made. A specific 
gravity of 1030 is not very rare. 



152 SPECIAL PATHOLOGY OF THE BLOOD. 

White Cells. 
A. Quantitatice Changes. 

Leucocytosis is absent in uncomplicated cases. In the series in 
Table VI. the occasional leucocytosis may be due to digestive or to 
a variety of other influences (uterine troubles, etc.), which could 
not be excluded. 

The average in Thayer's 63 cases was 8,467 and in Da Costa's 
7,090; in the present series it is just under 8,000. 

As in pernicious ansemia, the worst cases are apt to have leuco- 
penia, and as improvement progresses the white rise even faster 
than the red corpuscles. Thus in Romberg's careful study of 117 
cases, 24 cases w^hose haemoglobin was under 40 per cent had an 
average of 6,350 leucocytes per cubic millimetre, while 52 cases 
whose haemoglobin averaged 60 per cent had an average of 9,250 
leucocytes. We found the average in healthy girls of the same 
age to be 9,068 white cells per cubic millimetre. 

The absence of leucocytosis is tlie most important point in dis- 
tinguishing chlorosis from secondary ansemia due to cancer, suppu- 
ration, etc. 

B. Qualitative Changes. 

Lymphocytosis is usually present, as in pernicious ansemia, when- 
ever the disease is well marked, and sometimes even in mild cases. 
Thus Rieder found in 12 cases an average of 33 per cent of lympho- 
cytes, the highest percentages being 53.7, 43.5, and 41.7; but Da 
Costa in 37 cases found rather low figures for the small lymphocytes. 
In his series eosinophiles were notably decreased, and in 70 per 
cent of his cases entirely absent. Either the small or the large 
lymphocytes may predominate. In my own experience it has 
usually been the small forms, while Da Costa has found an aver- 
age of 15.5 per cent of large mononuclear forms (including large 
lymphocytes) in his 37 cases. In one case he made out 40 per cent 
of these cells with only 32 per cent of polymorphonuclear. 

The neutrophiles suffer proportional!}', their low percentage con- 
trasting often with that of secondary ansemia associated with leu- 
cocytosis. Eosinophiles are occasionally increased. In Rieder"s 
12 cases the average percentage was 3.5, the highest percentages 
being 9.6 and 7 per cent. 

Myelocytes are rare but have occasionally been observed in small 
numbers. 



THE PRIMARY ANEMIAS. 153 

Regeneration of the Blood. 

As the patients begin to mend under the influence of treatment, 
the blood changes are just the reverse of those seen during the de- 
velopment of the disease. First the corpuscles gain in numbers, 
the haemoglobin still remaining low; later and much more slowly 
the coloring matter, size, and weight of the cells are renewed. It 
seems as if the new-formed cells were of light weight and had to 
be replaced gradually by cells of normal stature. The nucleated 
corpuscles and deformities disappear and the leucocytes shoot up 
often a little above the normal. 

Blood Plates. 
They are considerably increased. 

Chlorosis without Knoivn Blood Changes. 
Romberg quotes the following facts: Three girls, nineteen, 
twenty, and twenty-five years of age, came to him with typical 
symptoms of chlorosis. Their blood counts showed : 

I. Eed cells, 5,246,000 ; Hb. 80 per cent. 

II. " " 5,376,000; " 83 " 

III. " " 4,408,000; " 87 '' 

All improved markedly under iron treatment. 
I mention this because I have seen several similar cases and 
have heard of others from colleagues. 

Summary. 

1. Blood as a whole : Very pale in marked cases, very fluid, but 
coagulates rapidly. Fibrin not increased. Specific gravity usually 
low, running parallel with the haemoglobin. 

2. Red cells: Average 4,000,000 when the patient is first seen, 
very rarely go below 1,000,000. The majority of them are small- 
sized, pale, often deformed. ISTucleated corpuscles are rare (normo- 
blasts as a rule). 

3. White cells not increased. 
Lymphocytosis, occasionally eosinophilia. 

4. Blood plates increased. 

Diagnostic Value. 
1. The points of difference from pernicious ansemia have been 
discussed (see page 140). 



154 SPECIAL PATHOLOGY OF THE BLOOD. 

2. It is important to distinguish it from simple debility, and 
from cases in which the skin only is anaemic ; in both of these con- 
ditions the blood is normal. 

3. From secondary anaemia it may be indistinguishable in case 
the latter be without leucocytosis. When leucocytosis is constantly 
present and the percentage of polymorphonuclear leucocytes is in- 
creased, chlorosis (uncomplicated) can be excluded. Of course 
many of the complications which may occur in chlorosis are accom- 
panied b}' leucocytosis. 



CHAPTER II. 

LEUKAEMIA. 

The distinction between leukaemia and leucocytosis lias been 
sufficiently dwelt on above. 

The blood of the vast majority of cases of leukaemia falls clearly 
under one or the other of two distinct types, myeloid on the one 
hand, hjmijltoicl on the other. Myeloid blood is found only in cases 
with great liypertiophy of the spleen, marked marrow changes, and 
little or no enlargement of the other lymphatic tissue. Such cases 
are usually chronic (two to five years). ^ Lymphoid blood, on the 
other hand, may be associated either with acute or chronic forms of 
the disease, the lymphatic glands may or may not be enlarged, and 
the spleen may be as big as in cases of the myeloid type. The 
diagnosis of leukaemia can easily be made b}^ the blood alone, but 
we cannot say from the blood whether or not the spleen or the vis- 
ible lymph glands are hypertrophied. In acute lymphaemia the 
lymph glands of the alimentary tract (cervical, faucial, gastro-en- 
teric, mesenteric) may be the only set involved, or the process may 
not involve the lymphatic glands at all. At least nine cases of this 
type have been reported, all of them acute and apparently originat- 
ing like the '" myeloid " cases from the marrow itself. The matter 
has been discussed and studied, especially by Walz,^ by Pappen- 
heim,^ and by Dorothy Keed.* 

All of the forty-nine cases associated with myeloid blood which 
have come under my observation have run a chronic course, while 
of the cases showing lymphaemia seven were chronic, five acute, and 
five subacute. All the myeloid cases had very large spleens with- 
out enlargement of visible lymph glands, but three of the lymphatic 
cases had spleens almost filling the abdomen. 

' But Grawitz (p. 333) and Reimann (Wien. klin. Woch., 1899, No. 39) liave 
reported cases which appeared to be acute. 

•'Walz: Centralb. f. allg. Path., 1901, p. 967. 

"Pappenheim: Virchow's Archlv, vols, clvii., clix., and clxvi. 

-* Dorothy Reed: Am. Jour. Med. Sc, October, 1902. See also Kelly: 
Trans. Assn. American Phys., 1903. 



156 



SPECIAL PATHOLOGY OF THE BLOOD. 



Tlie disease leukaemia, then, is associated with two types oi 
blood. 

1. Myeloid blood. 

2. Lymphoid blood. 

I. MYELOID. T.EUK.EMIA. 

The drop as it emerges from the puncture looks somewhat 
opaque in color, but is neither whitish nor chocolate-colored. It 
flows very sluggishly, however, and is difficult to spread between 
cover-glasses owing to the masses of white cells contained in it.^ 
Coagulation is normal, three minutes or less with Wright's coagu- 
lometer, and fibrin is not increased. 

Kki) Cells. 

■ In the earlier stages of the disease there is no anaemia. Later 
the diminution in red cells is moderate, averaging about 3,120,000 
in the forty-seven cases of Table VIL Toward the end of life the 
count of red cells often falls l^elow 2,000,000. The i)atients are 
often not pale and may feel perfectly well. The haemoglobin is 
usuall}' diminished, the color index being about 0.6 in my cases. 
It is difficult to read the v. Fleischl instrument in leukaemia, as 
the presence of so many leucocytes gives a muddy tint to the liquid, 
not easy to compare with the red of the glass. 

Tabi>e VII. — Leukaemia. 



No. 




Red Cells. 


No. 




White Cells. 


1 

2 


Highest, 


5,000,000 

4,877,000 

4,800,000 

4,592,000 1 

4.288,000 1 

4,140,000 i 

4,016.000 ! 

3,832,000 

3,760,000 

3,635.570 

3,605,000 

3,584,000 

8,572.000 


1 

2 


Highest. 


1.072,222 
980 000 


3 




3 




820 000 


4 .... 




4 




800 000 


5 




5 




756,000 
748.000 


6 




6 








7 




716,000 


8 




8 




656.000 


9 




9 




626 600 


10 





10 




570 000 


11 




11 




500,000 


12 




12 




492,000 


13 





13 





454,000 



^ Hence use a very small drop and warm the cover-glasses at the last mo- 
ment before the blood touches them. 



LEUKEMIA. 
Table YII, — Leukemia {Continued). 



157 



No. 




Red Cells. 


No. 




w Mte Cells. 


14 




3,400,000 
3,292.000 
8,232,000 
3,200,000 
3,170,000 
3,090,000 
3,080,000 
3,020,000 
8,078,000 
3,010.000 
2,996,000 
2,960.000 
2,952,000 
2,938,000 
2,921,600 
2,868,000 
2,792,000 
2,738,000 
2,715.000 
2,706,000 
2,628,000 
2,576,000 
2,520,000 
2,500,000 
2,322,222 
2,320,000 
2,256,000 
2,140,000 
2,112,000 
2,060,000 
2,016,000 
2.010,000 
1,866,664 
1,756,000 
1,420,000 
1,386,000 
1,358,000 
1,200,000 
408,000 

2,706,039+ 


14 




453,000 


15 




15 




448,000 


16 




16 




448,000 


17 




17 




430,000 


18 




18 




428,000 


19 




19 




420,000 


20 




20 




405,000 


21 




21 




400,000 


22 




22 




394,000 


23 




23 




386,000 


24 




24 




367,000 


25 




25 




340,000 


26 




26 .... 




324,000 


27 




27 




320 000 


28 




28 




290 000 


29 




29 




290 000 


30 




3o:::. ;;;:;•; 

31 




274,000 


31 




260,000 


32 


32 




260,000 


33 




33 




248,000 


34 




34 




236 000 


35:;;::;;;;::: 




85 




220 500 


36 




36 




213000 


37 . 




87 




188 000 


38 




88 




186,000 


89 


89 . 




183,000 


40 





40 




175,800 


41 


41 




170 000 


42 





42 




160,480 
14] 000 


43 ... 




43 




44 




44 




139 600 


45 .. 




45 




138,000 


46 


46 




134,400 
132,000 
111 000 


47 




47 




48 




48 




49 




49 


Lowest. 


98 000 


50 






51 




Avera2:e = 385.808 


52 

1 


Lowest, 
^.verage = 


i 
1 







Quiditatli-p Changes. 

The striking point is the presence of very numerous nucleated red 
cells, even in the absence of any sign of ancemia. With over 4,000,- 
000 well-formed and well-colored red cells, we may have hundreds 
of erythroblasts in ever}^ cover-glass. They are as numerous in 
this form of leukaemia as in the worst forms of pernicious anaemia, 
even though the. patient may be feeling nearly well. In Taylor's 



158 SPECIAL PATHOLOGY OF THE BLOOD. 

j'ases there were ten with 10,000 or less of the nucleated red cells 
})er cubic millimetre, three with 10,000 to 20,000, and two between 
60,000 and 70,000. One showed only 360 per cubic millimetre. 

Both normoblasts and megaloblasts may be seen, but in most cases 
the latter are in the minority. In nine cases studied by Da Costa the 
normoblasts averaged 4,654 per cubic millimetre and the megalo- 
blasts 1,257 Many of the normoblasts show fragmentation in their 
nuclei, and occasionaly true karyokinetic figures are seen. In the 
anaemic cases we find all the other changes in the red cells charac- 
teristic of anaemia, but the nucleated cells are almost always more 
prominent than in any other form of anaemia of a like severity. 
This shows that nucleated corpuscles are not to be thought of a> 
evidence (like deformities in shape) of regenerative or degenerative 
conditions only. A special connection to the wide circulatory chan- 
nels of leukgemic marroAv seems indicated, all the nujre so as in the 
lymphatic form of the disease in which th(^ bone marrow is usually 
much less affected, nucleated corpuscles are nuich less numerous, 
appearing in relatively small numbers in the very acute anaemic 
cases and not at all in those which are not anaemic. The proto- 
plasm of the erythroblasts is usuall}^ polychromatophilic, contrast- 
ing in this respect with the acidophilic protoplasm of embryonic 
and infantile erythroblasts. 

The variations in size and shape correspond to the degree «>f 
anaemia present ; occasionally, i.e., in cases seen early in the course 
of the disease, the red cells are quite normal. 

As the count of the white cells rises, that of the red may fall, 
and vice versa; or the red cells may remain at a comparatively high 
figure despite the progress of the white. 

White Cells. 
Qua ntltative CJi a nges. 

The average number per cubic millimetre in the forty-nine cases 
of Table VII. (the lymphatic cases being excluded) was 385,808 at 
the time when the cases first came under observation. The highest 
count in this series is 1,072,222 and the lowest 98,000. 

Among the older recorded cases are some in which the white 
cells were said to be more numerous than the red. The average 
ratio in my series is about one white to seven red. The highest 
ratio is 1 : 2, and the lowest 1 : 37. It is best to use the "red coun- 



LEUKiEMIA. 



159 



Table VIII. — Myeloid Leukemia. 









1 

' PERCENTAGE. 


S 

Si 

1 c 


11 
is 

S - 

f 




z 


1 


1 


1 
30 


% 
11 

P 


1 

s 
1 


t 

o' 

.a 

S 

i 
3 


i 


•1 
1 


f 


1 
1 


Date. 


1 


2,010,000 
1,720,000 

4,125,000 

4,016,000 
4,592,000 

2,960,000 
3,184,000 
3,156,000 
3,400,000 
3,670,000 
3,100,000 
3,080,000 
2,520,000 

4,016,000 

2,792,000 
2,715,000 
2,2%,000 
4,288,000 
2,921,600 
3,010,000 
2,996,000 
4,800,000 
3,060,000 
2,016,000 
2,576,000 
2,448,000 
2,120,000 

2,528,000 
5,120,000 
5,000,000 
4,800,000 
4,140,000 
2,82.5,000 
2,17.5,000 
2,952,000 
3,090,000 
3,020,000 

3,170,000 

2,706,000 

2,002,000 
2.631.000 


716,000 
732,000 
708,000 
253,900 
200,(KX) 
646,000 
448,000 

175,800 
264,000 
276,000 
111,000 
183,090 

mm) 

405,000 
510,000 
528,000 
.570,000 
.560,000 
800,000 
26,000 
139,600 
394,000 
340,000 
213,000 
492,800 
188,000 
134,400 
220,500 
274,000 
260,000 
748,0(X) 
168,800 
190,000 
188,600 
159,000 
134,000 
137.80(J 
138,000 
141,000 
410,000 
441,000 
324,000 
186,000 
4.54,000 

260,000 
317,000 
290,000 
260,000 
278,000 
289.0(X) 


40.0 


1.0 


10.0 


4.0 


42.0 


3.8 


Many 


Many 


Many 


Nov. 1st, 1897.1 
\ov 3d 1897 
























\ov I'^th 1897 


o 


.55 




















July 16tli, 1895. 
July 2.5th. 1895. 
Jan. 21st, 1897. 
Feb. 8th, 1897. 
Feb. 17th, 1897. 
July 1.5th,. 1897. 
July 29th, 1897. 
Aug. 5th, 1897. 

Aug. 10th, 1896. 
Aug. 31st, 1896. 
Jan 22cl 1896 




















3 


60 

42 
38 
40 

a5 

48 
40 
50 


;36.5 
46 
46.6 
17 


7 1 4.5 
1.514.5 
1.4il0.4 
3 11 


4 

1.5 
2.2 
19 


28 
3:3.5 
36.7 
49 


Many 


Many 


3 

2 

3 

13 


1 





31 




















4 
5 
6 


27.2 
31 


10.5 
15 


26 

8 


3 
5 


25 
32 


Many 


Many 






7 


72.2 
51 


\. 


3.6 

2 


2 

4 


17.4 
42.4 


Many 


Many 


5 


9 








Jan. 22d, 1896.^ 
























Jan. 23d, 1896. 
Jan 24th 1896 




















■ 




8 


.58 


55 


5 {4 


4 


34 


Many 


Many 






June 4th, 1894. 








Aug. 10th, 1894. 

April, 1893. Later 
the count of 
leufofvtes was 
normal for sev- 
eral months. 

Jan. 22d, 1896. 


q 


37 

ii 

42 

45 

78 


50.4 

44 

62.3 

53.8 

61 

37 

46 

62 

33 

26 

46 

45 

74.2 


18.9, .2 
1..5' 1 
3.8, 1.8 
2.2i 2.8 
3 i 

23 1 6 
1.5| 0.5 
1.5 1 


6.1 
2.5 
1.8 
14.4 
3 
8 

4 _ 
2.5 

% 

1.5 
3 

2.8 


24 4 










10 
11 
12 

13 
14 
15 
16 


51 

30.8 

IS 

;« 

26 
48 
33 
42 5 


8.8 










10 
8 
2 
3 

4 


11.5 

1 

0.5 

3 

4 










June, 1897 


17 
18 
19 


60 
.50 
46 

15 






4 


1 


Feb 22d 1896 








Feb. 25th, 1896. 




.53 

a5 

36 
40 

s 

35 
40 
31 
31 
35 
31 


61 

58 
48 
43 
33 
57 
47 

41 
53 

27 
24 
33 


6 
3 
17 
2 
5 
1.2 

3.8 

1.8 

3 

3.8 

4.4 


2.2 

18 
5 

3.2 
2.6 

'1.2 
1.4 
13 

12 
12 


2.5 
3.1 
3 

7 

4.2 
.2 

8.8 
8.2 
1.8 
1.2 
.4 


28 
35 

28 
28 
21 

28 

48 

43 
b3 
40 
45 
40 










Feb. 28th, 1896. 


21 

9^ 




14 
5.2 
•> 

2.4 
2.6 

15 

14 

11 


"\h" 


4 
4 
6 


i 

5 


5.4 per cent, of the 
lym p h c y t e s 
have the char- 
acteristics of 
Turck's •' Rei- 
zungsfornien." 

Oct. 4th, 1899. 

Oct. 21st. 
Nov. 3d. 
Nov. lOili. 


23 
24 

25 
26 


8 
1 

4 
1 
4 


2 





2 
3 
4 



* Many cells on border-line between large Ij^mpboc^'tes and m3'elocy tes and 
between these and polymorphonuclear neutropliiles. 
■^Cerebral hemorrhasre. Death Jamiarv 25th, 1896. 



160 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table VIII. — Myeloid Leukemia {Continued). 





1 

i 




Percentage. 


2. 

If 

£ 5 


2 




i 


1 
23 

L 

.55 


II 


1 

1 

"3 
3C 


1 
>> 

i 


1 

1 


1 


1 


i 
It 

,s o 

2 = 

1 = 


x| 1 Date. 

Ill 


37 

28 
29 
30 
31 
32 
33 
34 
35 
36 
37 


1,756,000 
2,500,000 

•:;■;:;:: 

3,832,f)bf.) 


347.900 
418,000 

248,000 



274.i)lKJ 

2«'>();io 


;i5 3 

41 2 

*>7 1 2 
32 1 4 
49.6 3.6 
30 110 
.54 i 8 
47.524.5 
36 4 
57.5 

42 5 
53.2 9.6 


5 
6 



4 

2.2 

.5 



5 

4 

1.5 

3 

1.8 


i 

9 

I 

5 

A' 

3.7 


.54 

48 

23 

55 

38.6 

45 

34 

36 
47 
27.6 





4.5 
10 

1,5 

2 

3,2 


25 
4.6 


2 
11 

4 
3 


3 
4 




First day. 

Phthisis also 
fourth day. 

Turck's " Rei- 
zunfrsformen" 
9.5 per cent. 

April 8th. 
April 10th. 
April 12th. 
April 14th. 
April 2d. 
April 4th. 
April 11th. 
April 22d. 
April 26th. 
April 28th. 
May 5th. 
Nov. 5th. 




301, (XHJ 

3.56.000 

3,572,000 2:36.000 

242.0(JU 

2,728,000 258,00:i 
3,22S.(X)0 186. (K 10 

220.0(10 

3,1 .28.000 oSii.iMM 
3.t>58,000 260. IK (11 
3..")S4.000 1(VI.4W) 
3.096.000 1:4.0:KI 
;{,232.0(XI 420.000 
3.22O.O00 320.0IH) 










t 










1 














38 


60 


68.61 3.1 


2.1 


1.3 


24.9 





6 







55 
45 
45 

4.") 

:}-■) 

;V) 
65 

40 
40 

1 


67.9 3 
68.8: 2.1 


4.1 

X 9, 


2.6 
2.4 


'>?. 6 




8 






•>1 q 


...... .,..., 


8 




















H5.6 3.1 ! 5.2 
01.5 12.1 8.2 
.^2 2 4.4 
49 7* .,.. 
.58.9, 0.9, 4.2 
63.2 5 ! 1.7 


1,1 
2,1 
1.6 
17 
1,1 
2,1 
1,5 
2.1 
1.9 


25 

16.1 

40 







6 
2 
15 
8 
3 
3 
30 
10 
12 












39 






3 

"6*" 

2 

10 
8 
2 








Nov. 9th. 


40 


33.1 
29.5 
33.5 

.30.8 
28.6 


1,4 




March 30th. 
April 7th. 


41 


2,628,000 
2,228,001) 

3,123,000 


448,000 
4 IS. 21 10 
4<J4.OO0 

325,000 


49 

52.4 

44.2 


L5 
3.9 
10.2 


14.5 
10.8 
15.1 


'.'.'.'.'.'. 




April 22d. 
April 26th. 
April 28th. 
May 4th. 


Av. 


|43 


47.5 


5.2 


5.4 


4,4 


32.5 


5 











* Large and small lymphocytes counted together. 

ter " with a dilution of 1 : 200 in counting the white cells, otherwise 
they are often too crowded for convenience. Hayek ^ and Da Costa ^ 
have shown that the leucocytes may vary enormously in a few hours; 
e.g., 10 a.m., 122,500; 4p.m., 235,000; or again, 10 a.m., 730,000; 
4 P.M., 547,500. 

In the fresh specimen we notice that a large proportion of the 
white cells are but slight!}^ amoeboid, a point of marked contrast 
with leucocytosis, in which the leucocytes are actively amoeboid. 
This is due to the fact that the myelocytes which form so large a 



1 Hayek: Wien. khn. Wocb., 1897, No. 30. 
-Da Costa: Loc. cit., p. 251. 



LEUKEMIA. 161 

portion of the leucocytes in this disease possess little power of 
amoeboid motion. 

With or without the influence of therapeutic agencies or after 
splenectomy the white cells may fall gradually to normal and re- 
main there for some time. The patient's symptoms may simulta- 
neously ameliorate, or there may be no improvement but rather the 
reverse. Such a case occurred under my observation, and the pa- 
tient, a washerwoman, w^ent back to work and afterward passed 
through an attack of lobar pneumonia in safety. 

At such a time, when no increase in the white cells is present, 
we should never suspect leukaemia, seeing the case for the first 
time, unless we chccuce to make a differential count; then the char- 
acteristic qualitative changes (see below) may be found, or the 
blood may be wholly non-leuksemic, as in a case recently reported 
by McCrae, and in a similar case slides from which were recently 
shown me by Martin. 

Qualitative Changes. 

1. Myelocytes. 

The enormous number of myelocytes is the chief point of int Br- 
est. The average in my 41 cases was 32.5 per cent (see Table YIIL), 
rising in one case as high as 60 per cent and only 4 times falling 
lower than 20 per cent, but the}' may fall as low as 7.1 per cent 
(31,950 absolutely), as in one of Da Costa's cases. 

Taking the average total number of leucocytes as 325,000 per 
cubic millimetre, the absolute number of myelocytes averages over 
123,000 per cubic millimetre. So far as I am aware, the highest 
count of myelocytes in any other disease is that mentioned on page 
438 in a case of malignant disease, namel}", 4,514 per cubic milli- 
metre, i The contrast is sufficiently striking. I wish to insist upon 
this point, namely, that the blood of myeloid leukaemia is abso- 
lutely peculiar and characteristic, and could not possibly be con- 
fused with that of any other disease. Certain writers of late years 
have concluded that because mj^elocytes do occur in a great variety 
of diseases other than leukaemia, therefore there is nothing pecul- 
iar about the blood of the latter affection. It would be as logical 
to say that because albumin and casts occur occasionally in the urine 

' Taylor reports a gastric cancer witli 4,285 per cubic millimetre. 



162 SPECIAL PATHOLOGY OF THE BLOOD. 

of persons practically well, therefore there is nothing characteristic 
about the urine of acute nephritis. 

At the first glance the stained specimen of leuksemic blood 
seems to be composed mostly of myelocytes, but this is because they 
are on the average so much larger than the other forms of white 
cells, which, being packed away in the interstices between the large 
myelocytes, do not appear prominently at first sight. 

Although (as just mentioned) the average size of the myelocytes 
is greater than that of any other kind of leucocyte, there is a great 
range of variation in their size, and some are hardly, if at all, larger 
than a red cell. (This is equally true of the myelocytes as seen in 
the bone marrow. See page 65.) 

The individual characteristics and variations in the myelocytes 
have been already sufiiciently described on page 64. 

^. Polymorphonuclear Cells. 

Absolutely the number of chese cells is greatly increased, al- 
though the number in each 1,000 leucocytes is considerably dimin- 
ished. The actual number per cubic millimetre averages over 
200,000 in my series, and in all but one of Taylor's 17 there were 
65,000 or more. The average percentage in the 41 cases of Table 
yill. is 47, the figures ranging between 17 and 72 per cent. 

The individual cells show a much greater range of variation in 
size, staining properties, and the size and shape of the nucleus than 
in any other condition. In most forms of leucocytosis, for example, 
one polynuclear cell looks very much like another, but in this form 
of leuksemia we are often struck by — 

(a) Very small cells or very large cells (4 // to 20 ,a in diameter). 

(I)) Dark-stained or Y&i:j pale- stain eel cells. 

(c) Unusual shapes in the nuclei. 

(d) Variations in the size and staining of the granules. While 
normal polynuclear cells have granules nearly of one shade, the 
leuksemic polynuclear cells have granules varying from yellow or 
pink to purple or blue. Their size also varies greatly. Taylor 
found some as large as eosinophilic granules. 

Besides these variations, we often see cells apparently belonging 
to this type, but whose protoplasm shows no color or granulation 
whatever. Other cells show a few granules scattered about against 
a perfectly white background. Such cells may contain basophile 
granules besides the neutrophile. 



LEUKAEMIA. 163 

(e) There are always some cells on the border-line between the 
polymorphonuclear and the myelocyte, and in regard to which de- 
cision must be arbitrary. I have lately been in the habit of classi- 
fying such cells as Transitional Neutropliiles. Similar cells are 
found in leucocytotic and anaemic blood (see page 102.) 

S. Lymphocytes. 

In percentages the lymphocytes are reduced from their normal, 
20 to 30 per cent, to an average of 10.6 per cent, as in leucocytosis. 
But still if we class together large and small forms, their absolute 
number is always increased. Thus the lowest percentage present in 
Table VIII. (namely, two per cent) would mean 6,500 out of the 
average 325,000, the total leucocyte count per cubic millimetre, and 
this is three or four times as many lymphocytes per cubic milli- 
metre as are present in normal blood. 

The proportion of large and small forms varies a great deal. 
Da Costa found an average of 12 per cent large and 4.5 per cent 
small in his 12 cases. Sometimes the lymphocytes in this form of 
leukaemia do not differ from those of normal blood, but in most 
cases we iind the following atypical varieties : 

{a) Large lymphocytes with a protoplasm so darkly stained that 
it is difficult to distinguish them from myelocytes. Indeed in some 
cases, when hints of a granular look appear in the violet-stained 
rim, we find it impossible to be sure whether we are dealing with a 
large lymphocyte or a myelocyte. The personal equation alone 
decides. These cells are not peculiar to leukaemia. Tlirck has 
described them (under the name of ^^ Reizungsformen") in most in- 
fectious diseases, and I have often seen them in the blood of ma- 
lignant disease and of pernicious anaemia. Taylor and Weil class 
them as myelocytes without granules. 

(h) Cells like lymphocytes except that thej^ contain a varying 
number of granules of one or more varieties (basophilic, acidophilic, 
or neutrophilic). 

4. Eoshiophiles. 

Like all the other varieties these are absolutely much increased 
Kelatively — by percentages — they may or may not be so. In my 
series they ranged from 1 to 19 per cent, averaging 4.4 per cent, a 
slight increase over the normal. 

Many writers, wrongly interpreting Ehrlich's observations on. 



164 SPECIAL PATHOLOGY OP THE BLOOD. 

tliis point, have stated that an increased ^jercentofje of eosinophilic 
cells was tlie distinguishing mark of leukaemia, and even recent 
writers {e.g,, Gilbert, Strumpell) contiinie to repeat this false 
statement. 

The cell most characteristic of sjylenic- m i/eloyenoas hukn'mui Is 
not the cosinophile hut the myelocyte. Nevertheless eosinophiles are 
enormously increased absolutely, and this fact may be of great diag- 
nostic value. In a case of cancer of the marrow with anaemia and 
leucocytosis Epstein ^ found large numbers of inyelocytes and nu- 
cleated red cells, but no eosinophiles. The absence of eosinoi)hiles 
in this case sufficed to exclude leukaemia. ■ 

We distinguish several types of eosinophiles in leukaemic blood. 

{a) Ordinary (polymorphonuclear) eosinophiles. 

(&) Eosinophilic dwarf cells and giant eosinophiles. In some 
of these the granules are also huge — even 2 //. in diameter (Taylor). 

(c) Eosinophilic myelocytes. 

{a) Needs no comment ; {h) is simply a very small cell with 
eosinophilic granules ; sometimes such cells are not over 5 ,a in 
diameter. They are not uncommon in this form of leukaemia 
and are very rare in any other disease. The same is true of 
(<:?), the eosinophilic myelocytes which are very rare in anj' other 
disease, except pernicious anaemia, in which they are occasionally 
seen. 

These cells are like myelocytes except that their granules are 
eosinophilic instead of neutrophilic (see Plates I. and II.). The}' 
are found in the marrow in considerable numbers and ma}' consti- 
tute the majority of the eosinophilic cells in this form of leukaemia. 
Occasionally we see eosinophiles with a fcAv basophilic or neutro- 
philic granules as well. Eosinophilic myelocytes are of constant 
occurrence and great diagnostic value in leukaemia. In no other 
disease are they equally numerous. Their size, like that of the 
neutrophilic myelocytes, varies from 8 to 25 ,a diameter. 

5. Basophiles. 

{a) The lymphocytes may contain basophilic granules as in any 
ordinary blood. 

'Epstein: Zeit. f. klin. Med., 1896, vol. xxx. 

2 Yet Hirschfelt and Alexander (Berl. klin. Woch., 1902, No. 11) report a 
case of myelogenous leukaemia (with autopsy) in which both eosinophiles and 
mast cells were absent from the circulatino; blood. 



PLATE TT. 

Fig. 1. — Both this and Fig. 2 are intended to be fac-similes of actual micro- 
scopic fields. 

(a) Note the cell between those labelled 8 and 9 — apparently a "mast cell.'' 
Such cells are often seen in this form of lenka-mia. With Elirlich's stain lliey 
present this appearance. Basic stains bring out coarse blue gi'anulcs in llie 
periphery of the protoplasm. 

(/>) Note also the cell at the extreme upper right-hand corner of Fig. 1, 
which it is almost impossible to classify either as a myelocyte or as a poly- 
morphonuclear neutrophile, since it (tppearfita be intermediate between the 
two varieties. 

{(') Both the nucleated corpuscles are normol)lasts ; 9 has ]")oly^-liromatopliilic 
protoplasm. The led cells show scarcely any deformities and very slight de- 
ficiency in coloring matter. 

Fig. 2. — {a) Note the deformities in size and shape of red corpuscles, owing 
'-0 the anaemia present. 

(/>) No lymphocytes are figured, as they made up oidy two per cent of the 
white cells in this case. Eosinophiles were absent. 

{(') Note that the contrast between this figui'c (leucocytosis) and the one 
above it (leukipmia) is not in the abundance of white cells but in the lii((l of 
white cell predominating among those present. 



Examination of the Blood. 



PLATE II. 



Figure I ■-= Splenic-myelogenous Leucaemia 
Figure 11 = Leucoeytosis (cancer of kidney) 
Cells stained yellow =^ Red corpuscles 

1. 2. 3. 4 a. 5 = Polymorphonuclear neutrophilee 

6 — Lymphocyte 

7 a. 8. = Eosinophiles 

9 a. 10 = Nucleated red corpuscles 

All others = Myelocytes 



Figure I 
Leucaemia. 




4>f.' •■■If V ' ■- ^ ■^iF* 


















"^ 



fe» 



Cells stained yeJlo'i 
All others — - 
Polymorpho- 
nuclear- 
neutrophiles 



Figure II 
Leucocytosis. 



Red corpuscles 
V 







\ 



Scale of 



R. C. Cabot fee. 



Lith. Anst. V. E. A. Funke, Leipzig. 



LEUKEMIA. 165 

(b) The basopliilic or aniplioteric tendency of the granules of 
some of the myelocytes has been already described (page 64). 

(c) '^ llastceUen /^ or coarsely granular basophiles, usually with 
a trilobed nucleus, are almost always to be found in specimens 
stained with Wright's stain. With the triple stain their proto- 
plasm is nearly unstained, but usually a number of round tvJiite spots 
can be made out against a faintly stained background. These are 
the basophilic granulations. Mast cells make up from one to ten per 
cent of the leucocytes in most cases of myelocytaemia. Ehrlich states 
that they are always present and greatly increased in such cases, 
but my experience and that of Taylor do not confirm this. In 2 of 
Taylor's 11 cases mast cells were absent. On the other hand, one 
of his cases showed over 140,000 mast cells per cubic millimetre 
(10 per cent), and it is undoubtedly true that "an excess of mast 
cells is one of the most trustworthy signs of myelogenous leukaemia." 
Their granules are not purely l^asophilic but metachromic. 

6. Mitoses, 

Leucocytes showing mitosis are very rarely found in leukgemic 
blood and play a negligible part in the increase of the circulating 
leucocytes. They have no value in diagnosis. 

7. PoIymorj)ho2is Condition of the Blood. 

Weiss has rightly insisted on the fact that in this type of leu- 
kaemia the blood preparations show a very polymorphous condition. 
There are no fixed types, but every variety shades through inter- 
mediate forms into some other variety. No two cells are alike. 
Precisely the same conditions obtain in the normal marrow, and we 
can scarcely resist the impression that in this form of leukaemia we 
see in the blood unfinished cells of various kinds which usually 
do not appear in the circulating blood. 

As Charcot-Leyden crystals have no diagnostic value and are not 
peculiar to any disease, no description of them will be given here. 
They appear to be present wherever eosinophiles are plentiful, e.^., 
in asthma, gonorrhoea, in the bone marrow, etc. 



166 SPECIAL PATHOLOGY OF THE BLOOD. 



8. Kemissions. 

During remissions, when the leucocyte count may fall to nor- 
mal, the iDercentage of myelocytes usually remains large and the 
diagnosis could thus be made even if we saw the case then for 
the first time. This I have observed in two cases, and Thayer and 
Taylor have had the same experience. But occasionally myelocytes 
and all other evidence of leukaemia disappear, and diagnosis in such 
remissions is impossible. JMcCrae and ]\[artin have studied such 
cases. During such "remission" occurring in anaemic cases the 
blood may take on almost or quite all of the features of pernicious 
anaemia. Two such cases have reeenth' been reported by Stengel 
{Med. Neius, October 20th, 1902). 

9. Atypical Forms. 

Schwartz {Zeit. f. HeWk. , November, 1901) has studied a case 
which at the first examination showed 40,000 leucocytes, 87 per 
cent of which were pclynuclear, with 7 per cent Ijanphocytes and 
6 per cent eosinophiles. Erj-throblasts were numerous. Later 
myelocytes appeared and the erythroblasts disappeared. 



II. LYMPH.EMIA. 

{Li/nqjli at'ir LeulctriN ia . ) 

The cases may be acute or chronic. 

The writer has watched seven cases of typical lymphatic leu- 
kaemia for periods of from seven months to three years. One pa- 
tient came over thirt}^ miles from time to time to report. His 
blood showed little variation from the following figures : Eed cells, 
2,300,886; white cells, 112,000. The diiferential count always 
showed the overwhelming majority (over ninet}' per cent) of small 
lymphocytes characteristic of the disease. The lymph glands were 
all much enlarged, the spleen just palpable. The patient kept about 
his work as gardener for over two years. Another, in an active 
wine merchant, was wholly unattended with symptoms. The pa- 
tient first sought advice for the unsightlj' glands in his neck. He 
continued to feel absolutely well and to work hard until life was 



PLATE B. 



Fig. 1. — Shows Normal Ked Cells and Sixteen Polynuclear Leucocytes, 
the latter drawn someAvhat too large in comparison with the red cells. 

Fig. 3, — From a Chronic Case. In some acute cases the lymphocytes 
are lararer. 



Examination ofthe Blood. 



Plate B. 




Hg.l. LzUCOGTrrOSIS,- ;.' 50000 per cu.m.ra.) 
("TO:ight's modification of leisTunans stain.) 




^1^.2. LYlylPfiAEMfA, ( LyMPHA.TIC LfUC AHMIA) 

m. = inegaloilast. e. = eosinophile p = polymiclear. 

The rest of the white .cells die lymphocTtes. 
(■Wiight's modification of LeisTiman^ stain.) 



GeoJiWdier 8. Co.,Iit}i,3i 



LEUKEMIA. 167 

suddenly cut sliort by an attack of pneumonia. I watched his blood 
for three years, and it always showed typical lymphaemia without 
anaemia. Grawitz has watched a similar case for over four years. 

The blood of acute lymphsemia differs as a rule in many cases 
from that of the chronic types. These differences will be referred 
to later on. 

Eed Cells. 

The count of red cells is often somewhat lower than in the 
splenic-myelogenous form of the disease, averaging 3,600,000 in my 
cases. In acute cases it is usually very low and the anaemia pro- 
gresses rapidly. In the infantile cases collected by McCrae, the 
highest count was 2,350,000. In chronic cases the red cells behave 
about as in myelocythaemia, except as regards nucleated forms. 

A point of interest m chronic cases is the 7'ainty of nucleated red 
cells, the abundance of which is so marked a feature of splenic- 
myelogenous leukaemia. They may follow the grade of anaemia 
present. In other cases (as in one reported by McCrae) nucleated 
red cells are entirely absent, despite a reduction of the red cells to 
1,680,000. In the eleven cases in infants collected by McCrae, 
there were no nucleated red cells found in seven. In acute cases 
the number of nucleated forms is often greater and may be as great 
as in myeloid leukaemia. Two cases recentlj^ reported by Herrick ^ 
exemplify this. 

White Cells. 
Quantitative Changes. 

As a rule the numerical increase is not so marked as in the 
splenic-myelogenous form. The average ratio of white to red cells 
is about 1 : 50 instead of 1:7, and we rarely see counts reach the 
height common in the other form of the disease. The highest count 
of my series was 1,480,000 at the patient's first visit, and the low- 
est 30,000, the average being 350,000 as compared with 438,000 in 
the myeloid leukaemia. These figures refer to uncomplicated cases. 

^ Journal of the Ainericau Medical Association, July 24th, 1897, 



168 



SPECIAL PATHOLOGY OF THE BLOOD. 



Qualitative Changes, 

1. Lymphocytes (small forms, large forms, or a mixture) make 
up usually over ninety per cent of all the leucocytes present. In 
some cases they are all nearly of one size, while in others we find 
every gradation from the smallest to the largest, so that it is abso- 
lutely futile to attempt to separate them into "large " and "small." 
Four of my cases were made up wholly of the small forms, all 
under 10 // in diamefpr, two were composed largely of forms over 
15 !>. in diameter, while six sliowed every intermediate size. 

Table IX. — Lymphatic Leukemia. 



No. 


Red cells. 


White 
ceUs. 


4 


t 


1 


11 


2 


1 

1 


1 ' 

c 


s 

i Remarks. 

1 
3 


1 

2 


4,877,000 

913,000 

1,440,000 

1,336,000 
1,100,000 

3,000,000 
3,500,000 
3,608,000 

4,700,000 
3,100,000 

3,960,000 
4,160,000 
3,768,000 

3,530,000 
3,653,000 

3,477,500 
4,078,000 

4,196',666 
3,612,000 
3,383,000 

5,837,000 
5,630,000 

3,50b",666 

5,178,000 


133,000 
33,000 
43,600 

93,000 
130,000 

31,600 
31,500 

38,500 
40,000 

31,500 

40,000 

3,400 

800 

1,480,000 

80,000 

77,500 

51,800 

79,500 

64,000 
164,000 

167 500 
90,300 
738,000 
708,000 
723,000 
760,000 
176,000 
393,000 

124,000 
180,000 
500,000 
800,000 
800,000 

20,000- 
60,000 


ii' 

23 

20 


75.8 

15. 


16. 
82. 


4.6 
2.4 


1.6 
.1 


2. 
,5 


4 ] 


L Subacute ; ten weeks. 
. Jan. :i4th, 1896. 
Jan. 26th, 1896. Acute 




25.4 


73.2 


.5 


.1 


.8 


3 1 


two weeks. 
L Jan. 27th. 
Jan. 38th. Death ; au- 


3 


5) 


68.5 

78. 


28. 

15.6 

* 


3.2 
5.6 
4.3 


2 
"3 


'*!6 




. April 3d, 1896. 

. April 5th, 1896. 

. April 6th, 1896. 

. April 7th, 1896. Acute ; 

five weeks. 
'April 8th, 1896. 
. April 12th, 1896. 
. April 32d (sepsis — semi- 

comatose) . 
April 39th. Death. 




....i::::. 






' 






95.5 


* 


4. 


.5 


.... 


2 2 




■56' 


39. 

94.7 
87.9 
80.5 
88.7 


52. 

* 
12. 
2.1 
1.6 


9. 

5.3 

.1 
17.2 
9.4 
















4 






(] 


March 31st, 1897. Chronic. 


5 


■:. 


2 




. Oct. 36th, 1896. Chronic. 
. Nov. 5th, 1896. 
Nov. 7th, 1896 






90.4 


1.4 


8. 


.2 






. Nov. 15th, 1896. 
Nov. 17th. Died Decem- 


6 


60 
45 

40 


94. 


9213 


6 
3.2 








ber, 1897. 
Chroni". 


7 





3.5 


6 1 


Positi\e Widal reaction, 
typhoid? — 1,000 leuco- 
cytes counted^ 

Second day. 
















Third day. Death. 


8 


41 


98.6 


* 


.8 


.6 








July 31st; 500 cells counted. 
July 33d. 


9 

10 

11 

12 

13 


39" 
40 
40 

j95^ 
95 

55 
40 

95 


99.2 
98.1 
61.4 
50. 

94. 
98. 
97. 
99. 
99.99 

80-90 


* 

1.3 
U. 
47. 







5-8 


.8 

.5 

4.6 

2.8 

6 

1.9 
3 
.8 
.0001 

10-15 



.1 
0^ 



.1 


.2 







.1 
















1 











Aug. 5th: 500 cells counted. 

Oct.; 1,000 ceUs counted. 

Oct. 33d; 500 cells counted. 

Nov. 16th; 500 cells 
counted. 

Nov. 34th, 1898. 

Mav 26th, 1900. 

Sept. 28th, 1900. 

Nov. 23d, 1900. 

One polynuclear in 8,0001 
All the rest = lympho- 
cytes. 

Examined once a month 
for three years ; excellent 
health throughout ; died 
of pneumonia, Feb., 1901. 



LEUKAEMIA. 



169 



Table IX. — Lymphatic Leukaemia {Continued). 



No. 


Red cells. 


White 
cells. 


11: 

"^ 2 

.... 

*i6' 

25 

40 
40 
55 
50 
50 
54 


1 

:::: >■• 
-7. £. 

9^0 

97.9 

86.2 

72. 

99.6 

92.2 

99.8 

86.5 

87.25 

81.5 

76.75 

87.64 


>> 


u 
II 

I'l 

1.4 
9.8 

28. 

.4 

7.8 

.2 

7.5 

8.25 

16.5 

18. 
7.5 


1 
.1 


1 

0.37 


1 

1 
1 

2 


1 


14 

15 

16.. .. 


■ mm 

3,870,000 
3,400,000 
2,384,000 
2,5.50,000 
3,656,000 

3,524,000 
3,170,000 


' 6bb',6()6 
730,000 
131,600 
111,000 
168,000 
154,000 
129,000 
124,000 
91,000 
87,000 

240,000 + 


* 

7. 
7. 

"i" ' 

* 

* 

5.5 
4.25 
1.5 
4.5 
3.7 


17 

18 






Few'. 




19 






20 

21 

22 


■ '.25 
1.2 




3 
2 

4 
2 


"i 




54. 




25.2 


16.4 




.6 




1 


6 




















Av'age 


40 


80.2 


15. 


4.2 


.2 


.4 







Remarks. 



Chronic. 

Acute. 

History unknown. 

History unknown. 

History unknown. 

History unknown. 

2.5(JU cells counted. 

July 21. 

July 27. 

AufT. 6. 

Aug. 12. 

Sept. 29. 

Sept. 29. 

Oct. 1. 

Oct. 3. 

Oct. 6. 



* Large and small forms counted together on account of the impossibility of difEerentiating 
them in these cases. 

In acute cases, in which the large cells usually predominate, 
the staining is often very faint throughout the nucleus and proto- 
plasm (see Plate III., h), so that at first sight we should think 
somethmg Avas wrong with our technique. Other leucocytes in the 
same preparation, however, will stain normally, showing that the 
trouble is in the lymphocytes and not in the technique. These 
large lymphocytes are identical in their appearance with those 
found at the " germ centres " of all adenoid tissue, and probably 
are the mother cells of the small lymphocytes. Benda has termed 
them " lymphogonien. " They have often been mistaken for mye- 
locytes, from which they are to be distinguished by the absence of 
any neutrophile granulation. They often show evidences of de- 
generation (see page 66). The protoplasm may be entirely un- 
stained as in most of the cells in Plate III., h^ or it may stain pale 
gray or pink. In other specimens, especially those of the small- 
cell type (Plate III., a), the lymphocytes stain well. Their nuclei 
are frequently indented or even divided in two (this occurs also in 
normal blood, but less often). 

Fraenkel believes that if a chronic case takes on acute symp- 
toms the blood becomes more lymphsemic, while if a case starts acute 
and becomes chronic the lymphocytes decrease. Thus a case re- 
ported by V. der Wey ^ of chronic myeloid leukaemia six weeks be- 
. iDeut. Areb. f. kliii. Med., vol. Ivii. 



170 



SPECIAL PATHOLOGY OF THE BLOOD. 



fore death began to have fever, hemorrhages, great increase in the 
total leucocyte count and in the anaemia. No comj^lication was 
present. The lymphocytes increased 30 per cent, and the polymor- 
phonuclear neutrophiles dropped from 30 to 3 per cent. 

Gerhardti watched a case which began acutely with a large 
percentage of large lymphocytes and then became chronic with a 
predominance of small lymphocytes. 

In acute cases Litten^ has noticed fatty degeneration in the 
leucocytes. 

The following figures illustrate the influence of a septicaemia 
(from suppurating cervical glands) which ended the life of No. 3 in 
Table IX. 



Date. 


Number 
of leucocytes. 


Percentagre of 
lymphocytes. 


April 3d 


31,600 

31,000 

28,505 

44,000 

31,500 

40,000 

Sepsis began. 

5,661 

4.000 

3,400 

3,222 

800 

471 


96 5 


« 4th 




*♦ 6th 


93.6 


8th 




** 10th 


95.5 


« 12th 




« 13th 




« 20th 




« 21st 




" 22d 


92. 


" 24th 




** 28th 




•* 29th 


94.7 


Death on 


the 29th. 





ZeissPs case, also of the lymphatic form, showed the following ; 



Date. 


White cells. 


Percentage of 
lymphocytes. 


Percentage of 
polynuclear cells. 


September 9th 


80,000 
113,000 
119,000 
122,000 
140,000 
Pneumonia began. 
119,000 

98,000 

68,500 

43,500 

50,000 

9,350 

133,200 

172,000 


96. 

97.8 
99. 

88.7 
85.4 
75. 


. 4. 


24th. 




26th 




29th 


2. 


October 6th 




" 9th 


1. 


" 10th 




" 11th 




" 12th 

" 13th 

" 14th 


11.3 


" 15t,h, 


14 6 


" 16th (A.M.) 

" 16th (P.M.) 


25. 



» Fifteenth Cong. f. innere Med., 1897. 
2 Eleventh Conn:, f. innere Med., 1893. 



PliATE III. 



(a) Chronic Lymplimnin with Excess of Small Lymphoc3'tes. 

One polymorph ^nuclear cell is present. All the rest are 13'mphocytes and 
exemplify the variations in the morphology of the cell occurring in this and 
other diseases as well as in health, e.g., variations in the staining of the proto- 
plasm and nucleus, indentation and even division of the nucleus. 

Note that the scale of the whole of Plate III. is larger than in the other 
plates (see scale of u). 

(d) AcKte Lymph(cmia with Excess of Larrje L^'mphocj'tes. 

Note the lack of chromatin in both nuclei and protoplasm of large 13'm- 
phocytes. The plasma around them or their extreme edge took most of the 
stain. The brown tint of the red cells is due to underheating. Compare the 
colors with those in the figure above {a) in which the preparation was prop- 
erl3^ heated. 



Examination of the Blood. 



PLATE III. 









Sv 



A 




^ Q 





m 




>*-:«>; 



>«f^a;5>^ 






Lymphatic Leucaemia 

a. Small Lymphocytes in excess 

b. Large „ 



10 20 



Scale ot u. 



R C Cjibot fee. 



itli. A.u8t. r K. A. Fuiike. Leipzig. 



LEUKEMIA. 171 

Polymorphonuclear neutrophiles are absolutely as well as rela- 
tively diminished in most cases. Indeed they are often so scarce 
that one has to look through several thousand leucocytes before 
hnding one. There is nothing abnormal about them — ^a point of 
nuuked contrast with the neutrophiles in myeloid leukaemia. Eos'm- 
opldles and myelocytes are equally rare. 

SwmifYiary . 

The leading characteristics of leukaemic blood are as follows : 
(<•<) Myeloid leukwrnia. 

1. Eed cells about 3,000,000 ; nucleated forms very numerous. 

2. White cells about 450,000, of which 

3. Myelocytes form about thirty per cent. 

4. Every possible form of cell intermediate between the ordinary 
varieties is to be seen. ("Polymorphous blood.") 

(5) Chronic lyinphatw leukcemia. 

1. Ked cells about 3,000,000 or lower; nucleated forms rare. 

2. White cells about 300,000, of which 

3. Small lymphocytes usually form over ninety per cent. 

4. Myelocytes and eosinophiles very scanty, 
(c) Acute lymphatic leukaemia. 

1. Red cells mucli diminished; nucleated forms infrequent. 

2. Large forms of lymphocytes usually predominate ; many of 
them often show signs of degeneration. 

3. Neutrophiles and eosinophiles very scanty. 

Diagnostic Value. 

Leukaemia is distinguished by the blood examination from 

1. Hodgkin's disease: («) splenic, (b) glandular. 

2. Tumors of the spleen and vicinity {e.g., kidney or retroperi- 
toneal glands). 

3. Enlargements of the lymphatic glands from tuberculosis, 
syphilis, malignant disease. 

4. Hydronephrosis. 

5. Huge leucocytosis from any cause. 

6. Chronic malaria. 

7. Amyloid disease. 

1. Leukcemia and Hodgkin^ s disease (lymphadenoma or pseudo- 
leukaemia) o The pathology of the two diseases is identical but for 
the blood count. In Hodgkin's disease the • blood is normal, or 



172 SPECIAL PATHOLOGY OF THE BLOOD. 

shows only a moderate auaemia or leucocytosis (polymorphonuclear 
cells alone increased), and the diagnosis is easily made. 

2. Tumors of the spleen and especially of the kidney are very ajDt 
to be mistaken for lenkaemia. Within a single year I was asked to 
examine the blood in three cases of "leuksemia," all of which 
turned out to be malignant disease of the kidney. In all of these 
there was a large tumor resembling the spleen in the left hypoclion- 
drium, also a very large increase of white cells. In two of them 
the blood was examined fresh and the great number of white cells 
in the slide taken as evidence confirmatory of leukaemia. The 
stained specimen, however, showed only marked leucocytosis witli 
ninety per cent of polynuclear cells of the ordinary type and no 
myelocytes. Other large tumors of this region showed similar re- 
sults. Occasionally cases of leukaemia with numerous metastases 
are described as "sarcomatosis," and then it is asserted that the 
blood of leuksemia is identical with that of sarcoma. The source of 
the mistake is obvious. 

3. Adenitis with hj'perplasia due to tuberculosis shows usually 
normal blood ' and is thus easily distinguished from leukaemia. 
Leucocytosis is often present in syphilitic cases and still more 
marked in those due to cancer or sarcoma, but the counts rarely 
reach 30,000 and myelocytes are absent or ver}' scanty. 

4. One case of h ijdroneplirosis in which the distention of the 
sac was so great that it presented as a hard, solid tumor on the 
right hypochondrium, was taken for leukaemia b}'- a competent 
observer some years ago. The nonnul blood examination re- 
vealed the mistake, and excluded also Inalignant disease in all 
probability. The diagnosis was reached, however, only at the 
autopsy. 

5. Huge leucocytosis in pneumonia or malignant disease may 
cross the old boundary line of 100,000 wliite cells, beyond which 
none but leukaemic cases were supposed to venture. The diifer- 
ential count sets us right instantly, showing ninety per cent or so 
of the increase to be made up of ordinary polymorphonuclear 
leucocytes. 

6 and 7. The large spleen and cachectic appearance associated 
with chronic malaria and long-standing suppurations may be easily 
distinguished from leukaemia by the absence of anything more than 
anaemia and leucocytosis in the blood. 

' Sometimes marked leiicopeuia. 



LEUKEMIA. 



173 





Red cells. 


White cells. 


Lympho- 
cytes. 


Poly- 
nuclear 
leucocytes. 


Myelo- 
cytes. 


Nucleated 
red cells. 


Leukaemia (splenic- 


About 


450,000 ± 


About 7.6 


About 50 


About 37 


Very 


myelogecous) . 


3,000,000 




per cent. 


per cent. 


per cent. 


numerous. 


Leukaemia ( 1 y m - 


About 


100,000 ± 


About 96 


About 3 


Absent. 


Rare. 


phatic). 


3,000,000 




per cent. 


per cent. 






Hodgkin's disease 


About 


7,500 ± 


Normal. 


Normal. 


Absent. 


Absent. 


Tumors of or near the 


normal. 
Usually 


20,000 to 


Greatly 


Greatly 


Few if 


Few. 


spleen. 


diminished. 


40,000 ± 


decreased. 


mcreasea. 


any. 




Leucocytosis in gen- 
eral. 




May be over 
100,000 


Greatly 
decreased. 


Greatly 
increased. 


Few if 


Few 




any. 


at times. 


Chronic malaria 


Much 


Somewhat 


Usually 


Usually 


Few if 


Few. 




diminished. 


increased. 


increased. 


decreased. 


any. 




Amyloid disease 


Usually 


Usually 


Usually 


Usually 


Absent. 


May be a 




diminished. 


Increased. 


decreased. 


increased. 




few. 


Hydronephrosis 


Normal. 


Normal. 


Normal or 
decreased. 


Normal. 


Absent. 


Absent. 



Effect of Intercurrent Infections. 

There are on record about thirty cases in which leukaemia (acute 
or chronic) has been complicated with some intercurrent infection, 
with marked effect upon the blood in all but one. This single case 
was an acute rheumatic arthritis reported by Eichter in the discus- 
sion of Fraenkel's article in the Deutsche TnediciniscJie Wochen- 
schrift for 1895 (Nos. 39, 43, and 45), p. 639. Here the blood 
remained unchanged. 

Muller' s ^ case of lymphatic leukaemia was complicated by a 
septicEcmia, and the count of white cells rose from 180,000 to 400,000 
per cubic millimetre, with a marked increase in the percentage of 
polymorphonuclear cells. Here was a genuine leucocytosis added 
to a leukaemia. 

With the exception of these two cases, all those hitherto pub- 
lished have shown a marked progressive decrease in the total number 
of leucocytes without any change in the percentages of the different 
varieties in twelve, while eight showed, like Miiller's, an increased 
percentage of the polymorphonuclear cells despite the decrease in 
the total leucocyte count. 

Marischler,^ in a case of lymphatic leukaemia with cancer of the 
kidneys, found: 

1. At First. 2. Later. 

Red cells 3,450,000 2,400,000 

White cells 96,000 48,000 

Haemoglobin 50 per cent 30 per cent 

* Muller: Deut. Archiv fiir klin. Med., 1892, vol. 1., p. 47. 
^Wien. khn. Woch., July 23d, 1896. 



174 SPECIAL PATHOLOGY OF THE BLOOD. 

1. At First. 2. Laujr. 

Polymorphonuclear cells 15.6 per cent. 57.5 per cent. 

Sraalllymphocytes 83.3 " 40.0 

Large lymphocytes 1.8 " 1.6 " 

Eosinophiles 18 " .16 " 

Myelocytes .16 

Various infections — miliary tuberculosis, pneumonia, grippe, 
erysipelas, abscess kidney, septic lymph glands — alike decrease the 
leucocyte count or reduce it to or below normal. In one case a rise 
just before death was observed. 

Thus in Henck's case the leucocytes fell from 400,500 to 89,000, 
in one of Mliller's from 246,900 to 57,o00, in Kovac's from 67,000 
to 17,000, in Zeissl's from 140,000 to 9,350. I have already men- 
tioned a case of lymphatic leukaemia (page 170) in which the leuco- 
cytes fell from 40,000 to under 500, this last being on the day of 
death. In this case the percentages of the different varieties of 
leucocytes remained entirely unchanged. 

Herrick ^ reports a case complicated by acute streptococcus infec- 
tion in which the white cells were 60,000 at the time of death. 
How high they may have been earlier is not known 

It appears, therefore, that when an infection complicates leukae- 
mia we may have — ■ 

1. No effect (see case of rheumatic fever as a complication, just 
mentioned). 

2. A genuine leucocytosis on top, so to speak, of the leukaemia, 
with an increased percentage of polymorphonuclear cells. 

3. A decrease in the leucocyte count Avith or without an increase 
of polymorphonuclear cells. This decrease is by far the most com- 
mon result and may go far below normal as death approaches. 

Goldschneider ^ found that by the injection of splenic extract 
and other substances he could bring about a similar diminution in 
the number of leucocytes, but that, as in the case of intercurrent 
infections, this diminution was not accompanied by any improve- 
ment in the patient's condition, and death followed as usual. 

Abscesses occurring in leukaemic patients are filled with poly- 
nuclear leucocytes as ordinary abscesses are, and do not contain 
myelocytes. 

'^Loc. cit. 

* Discussion of Fraenkel's article. 



( 



hodgkin's disease. 



175 



HODGKIN'S DISEASE. 

{Pseudo-Leuhcemia , Lymphoma.') 

The diagnosis of this disease is impossible without the blood 
count. Yet the blood is in no way peculiar, but presents in most 
cases all the characteristics of the normal tissue. Its value is as 
negative evidence, telling us in a given case that leukaemia is absent. 

(I.) Transitions from Hodgkin's disease to leukaemia have taken 
place under the eyes of competent observers, but they are very 
rare. But few such cases are on record so far as I know — thkt of 
Fleischer and Penzoldt,' that of Mosler,' and one reported by 
Senator, Mn which two sisters came under observation, both suf- 
fering from Hodgkin's disease. One died of it ; in the other the 
blood changed to that of leukaemia before death." Wende (Amer. 
Jour. Med. Sciences, December, 1901) reports a typical example of 
this transition. 



Date. 


Red cells. 


White cells. 


Haemo- 
globin. 


Remarks. 


April 26tli.. 
July 10th . . . 


5,128,000 
1,936,000 


4,000 
34,000 


88 


Typical "Hodgkin's disease." 
Polynu clears, 68 per cent. 
Lymphocytes, 27 " 
Polynuclears, 3.4 " 
Lymphocytes, 95.5 " 



Posselt (Wien. kiln. Woch., 1895, p. 407) has presented a 
similar case ; on August, 1892, the leucocytes were 15,000, with 
60 per cent lymphocytes ; on April, 1893, the leucocytes were 
330,000, with 80 per cent lymphocytes. 

Doubtless many of the other cases supposed to exemplify a simi- 
lar transition were really cases in which a leucocytosis arose owing 
to some inflammatory complication. 

From the existence of these very rare cases of a transition to 
leukaemia, it has been supposed, especially by French observers, 
that Hodgkin's disease is simply an early stage of true leukaemia, 
and that this would always become apparent were it not that the 
patients die of some intercurrent disease before the signs of leukae- 

' Deut. Arch. f. klin. Med., vol. xvii. 

^Ziemssen's "Handbuch d. Path, und Therap.," vol. viii. 

^Berl. klin. Woch., 1882, p. 533. 

^ Askanazy has recently observed the transition in a case in which the 
blood was normal for two and a half years and then leukaemic for one and a 
half years under observation (quoted by Pinkus in Notlmagel's "Specielle 
Path, und Therap.," vol. viii.). 



176 SPECIAL PATHOLOGY OF THE BLOOD. 

mia have time to show themselves in the blood. One difficulty with 
this view is that there occur chronic cases which last from eight to 
ten years without any change in the blood. Another difficulty is 
that the transition is in fact rare, despite the relative frequency 
witli which tlie disease is met with. 

(II.) Probably many cases diagnosed as Hodgkin's disease are in 
fact cases of glandular hyjjertrophy due to syphilis or tuberculosis, 
and this fact lias led many to the belief that (/// cases called Hodg- 
kin's disease are in reality only syphilitic or tuberculous adenitis. 

In a considerable number of cases, however, tuberculosis has 
been disproven by careful inoculation experiments with the glandu- 
lar tissue, and there is no reasonable doubt that some cases, at any 
rate, are not due to tuberculosis or syphilis. Probably the diagnosis 
can never be made with absolute certainty during life.' 

(III.) The frequent occurrence of fever and other symptoms 
characteristic of an infectious disease has led some writers to class 
it as such. In a certain percentage of cases the disease (like leukae- 
mia) has run an acute course, lasting not more than six weeks from 
the hrst sj^mptoms to death. In some chronic cases the same sort 
of evidence of an infectious nature has been brought forward. Ul- 
cerations occur in the mouth and intestine, through which morbid 
products might gain admission. Various bacteria (pyogenic and 
others) have been found in the blood and tissues from time to time, 
but numerous negative examinations for micro-organisms are also 
on record, and the evidence is insufficient to establish the infec- 
tious nature of the disease. I^one the less, there is a growing ten- 
dency among the leading writers and observers in Germany and 
elsewhere to believe that the disease will ultimately be shown to 
be tuberculous. 

(IV.) Meantime most surgeons continue to regard it as a form 
of sarcoma and to treat it like malignant disease. 

The Blood. 

Whatever the nature of the disease, we find in the earlier stages 
of most cases normal blood, as will be seen in Table X. (cases 7 to 
23 inclusive). 

1 The recent monographs of Reed (Johns Hopkins Hospital Reports, 1902. 
vol. X., p. 133), Simmons (Journal of Med. Research, June, 1903), and Long- 
cope (Bulletin No. 1 of the Ayer Clinical Laboratory, October, 1903, Phila- 
delphia), have shown that there is a characteristic histological picture corre- 
sponding to Hodgkin's disease, and apparently to no other. 



hodgkin's disease. 



177 



Table X. — Hodgkin's Disease, 



d 
12; 


Age. 


1 


Red 

cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Kemarks. 


1 


28 


F. 


5,500,000 


64,000 


75 


Polymorphonuclear cells, 95 per cent. 
Lymphocytes, 5 per cent. 


2 





M. 


3,848,000 


39,200 


48 


Acute. Diff.* 500. Polymorphonuclear cells, 
95.2 per cent. 
Lymphocytes, 4.6 per cent. 


3 


2i 


F. 


4,886,000 


32,000 


53 




4 


19 


F. 


5,528,000 
5,160,000 


22,200 
25,400 




DifE. 200 cells. Polymorphonuclear cells, 86.5 






per cent. 
Six weeks later. Lymphocytes, 12,0 per cent. 
Eosinophiles, 1,5 . 


5 


19 


M. 


2,480,000 


20,200 


33 


Stained specimens normal. 


6 


26 






14,000 
21,200 


60 
50 


June 6th. 






5,148,000 


June 11th. Polynuclear, 92.8 per cent. 

Small lymphocytes, 3,6 per cent. 
Large lymphocytes, 3.0 
Eosinophiles, .2 " 
Myelocytes, .4 
No nucleated reds. Reds pale. Some 
few Irregular in shape. 


" 


28 




4,312,000 


12,000 


42 


Polynuclear, 90.5 per cent. 
Lymphocytes, 7.5 
Eosinophiles, 2,0 


8 


59 






8,500 


68 












9 


28 




3,760.000 


7,000 


65 




10 


34 




3,380,000 

3,512,000 

2,960,000 
2,828,000 


6,800 

6,700 

■■■6,3()d' 
7,900 
7,600 


40 


Polynuclear, 84.6 per cent. 
Small lymphocytes, 10.0 
Large lymphocytes, 3.2 
Eosinophiles, 1.4 " 
Myelocytes, .8 " 
Normoblasts = 1 
November 21st. T, 102°. 

Seclmblr ^Ih 1 ^^^ «t^*° P^^^^y- ^^^^^ r^^"' 
npppmbPr 8tS" ^ar in size. Tendency to di- 
DPceSber Sh 1" minished size. Few large. 
DS£27m:J Slight poikilocytosis. 




40 




32 

28 


11 


43 






6,200 
7,200 














February 19th. Count 300. 

Polynuclear, 89.0 per cent. 
Large lymphocytes, 2,0 " 
Small lymphocytes, 8.7 " 
Eosinophiles, .3 " 






12 


2,880,000 
2,650,000 


5,000 

3,800 
***5,*20d" 


30 


January 6th. Count 500. 

Polynuclear, 57.6 per cent. 
Small lymphocytes, 29,9 
Large lymphocytes, 12.5 " 
Eosinophiles, .7 " 
Mast cells,: .3 " 
Reds rather pale. Slightly trregii- 
lar in shape. 

January 13th. 

January 15th. 

January 31st. Polynuclear, 63,2 per cent* 
Small lymphocytes, 34.0 " 
Large lymphocytes, 2.8 " 
Eosinophiles, 0.0 ** 
Megaloblasts = 1.0 
Normoblasts = 0.0 
Reds as before. 




30 
30 



Difr.= Dteferential count of. 



12 



178 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table X. — IIodgkins Disease {Continued). 



i 


Age. 


Red 

1 1 ^"^- 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 








3,252,000 
2,012,000 


3.000 

3.400 
5,000 


3(J 

30 

26 


February 8th. Polynuclear. 55.4 per cent. 
Larc-e l\-niphocytes, 8.6 
Small lymphocytes, 36. 
Eosinophlles. 0. 
Reds as January 31st. 
Februarv 13th. Polvnuclear, .57.4 per cent. 
Small lymphocytes, 32.2 
Large lymphocytes, 6.4 
Eoslnophiles, 4.0 " 
Februarv 23d. Polvnuclear. 70 per cent. 
Small lymphocytes, 26 
I>arge lymphocytes. 4 
Eoslnophiles. 


13 


44 




2.336,000 
2,140,000 


3,400 
4,000 


30 
35 


May 4th. Count .5(X» cells. 

Pols-nuclear. 82.0 per cent. 
Small lymphocytes, 15.6 " 
Large lymphocytes, 2.4 
Eosinophlles, 0.0 
No nucleated reds. Reds stain rather 
palely. Little variation in size. 
Slight irregularity in shape. 
May 28th, Polynuclear, 70 per cent. 
Small lymphocytes, 18 
Large Ivmphocvtes, 12 
Eosinophlles. 
Reds similar to May 4th. 


14 


28 










Polynuclear, 69 per cent. 
Lymphocytes, 26 
Eosinophlles, 5 












15 


37 


M. 


5,990,000 


13,500 




Polymorphonuclear cells, 95 per cent. 
Lymphocytes. 5 






16 


25 


M. 


5.440.000 


9.500 


59 


Death: autopsy. 


17 


19 


F. 


5,724,0001 6,800 


43 1 Polymorphonuclear ceUs, 50 per cent. 
I Lyrhphocytes, 40 


18 


Adult. 


M. 


3,652,000 


5.800 





Diff. 300. Polymorphonuclear cells, 50.0 per cent. 
Lymphocytes, 45.3 
Eosinophlles, 1.3 
Myelocytes, 1.7 

Big spleen, pallor, nosebleed, debility. 


19 


29 


M. 


5,210.000 
3.840.000 


5,000 
5,600 




Two months later. 
Thi-ee weeks •' 




1,000,000 















20 


58 


M. 


2,820.000 


4,800 


60 Polymorphonuclear cells. SO per cent. 
Lvmphocvtes. IT 
Eoslnophiles. 3 


21 


21 


M. 


4,560,000 


4,oai 

5.800 










JJO 


23 


M. 


4,210.000 


3,332 


■ 


Myelocytes. 1 per cent. Big liver and spleen. 
Eoslnophiles, 4 






23 




M. 


3,800.000 


1.440 


67 


Diff. .500. Polymorphonuclear cells. riJ25 per cent. 
Lymphocytes. 28.00 " 
Eosinophiles. .75 " 
One normoblast. 


?4 








No 
leucocv- 

tosis. 




Diff. 200. Polymorphonuclear cells. 63.5 per cent. 
Lymphocytes. 36.5 
Eosinophiles. 1.0 

Many of the lymphocytes have two nuclei. 













HODGKIN S DISEASE. 



179 



Table X. — Hodgkin's Disease {Continued). 



z, 


Age. 




Red 

cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


?r^ 








No 
leucocy- 

tosls. 




Difl. 300. Polymorphonuclear cells, 41,7 per cent. 
Lymphocytes, 48.4 
Eosinophiles, 9.3 
Myelocytes, .6 












?fi 


4 


M. 




No 

•leucocy- 

tosis. 




Diff. 500. Polymorphonuclear cells, 60.2 per cent. 
Lymphocytes, 36.0 
Eosinophiles, 3.6 
Myelocytes, .2 
Two normoblasts. 








Ta 




F. 








Diff. 500. Polymorphonuclear cells, 92.6 per cent. 
Lymphocytes, 5.2 " 
Myelocytes, 2.2 
No eosinophiles. 










"^ 








No 

leucocy- 

tosis. 




Diff. 313. Polymorphonuclear cells, 62.3 per cent. 
Lymphocytes, 37.0 
Myelocytes, .6 " 













29 


28 


M. 


5,318,000 


11,800 


85 


Polynuclear, .51 per cent. 
Small lymphocytes, a5 
Large " 7 
Eosinophiles, 7 " 


30 


30 


M. 


5,280,000 


6,800 


55 


Diff. Polymorphonuclear cells, 76.0 per cent. 
Lymphocytes, 22.3 
Eosinophiles, 1.4 
Myelocytes, .3 

No nucleated red cells. 


31 


33 


M. 


4,616,000 


2,400 


70 




3? 








2,200 




Diff. Polymorphonuclear cells, 69 per cent. 
Small lymphocytes, 19 
Large '' 18 
Eosinophiles, 4 

Few normoblasts. 












33 


41 




3,520,000 


12,600 


47 


Polymorphonuclear cells, 69.0 per cent. Nov. 33d. 
Lymphocytes, 28.0 " 
Eosinophiles, 3.0 " 

Polynuclear cells, 70.2 per cent. Nov. 38th. 
Lymphocytes, 29.0 "■ 
Eosinophiles, .8 


3+ 


36 






21,300 


90 












35 


54 






23,425 


65 


400 cells. 








Polymorphonuclear cells, 81 per cent. 
Lymphocytes, 18 
Eosinophiles, 1 " 


36 


58 




4,373,000 


4,400 


75 




37 


6 




4,112,000 


17,200 


35 


Diff. Polynuclear cells, 80.1 per cent. 
Lymphocytes, 18.8 " 
Eosinophiles, 1.1 


38 


6 


.... 


1,296,000 


4,100 


22 


Diff. Polynuclear cells, 5.6 per cent. 
Lymphocytes, 94.2 
Eosinophiles, .2 " Autopsy. 


39 


55 






64,000 
66,000 
45,400 


55 


June 18th. 








" 20th. 
" 22d. 


40 


26 






11,100 


85 





180 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table X.— Hodgkin's Disease {Continued). 



^ 


Age. 




Red 

cells. 


White 
cells. 


Per cent 
h^enio- 
Rlobin. 


Remarks. 


41 


27 




4,480,000 


24,000 

32,000 

20.700 

5.700 

42.(XI0 


90 


August 8th, Diff. count 633 cells. 

Polynuclear cells, 84.7 per cent. 
Small lymphocytes, 4.1 
Large " 9.6 
Eosinophiles, 1.6 
Myelocytes, .4 
August 2ytb. 
" 30th. 
September 1st. 

2a, Diff. 

Polynuclear cells, 92,8 per cent. 
Small lymphocytes, 1.8 
Large " 4.9 
Eosinophiles, .5 "■ 
Nornioblast No. 1, 
Death. 


43 


56 






25,600 

25,400 
2:3,000 


75 


August 15th. 

Polynuclear cells, 34.6 per cent. 
Small lymphocytes, 58.8 
Large "• 5.4 " 
Eosinophiles, 1.2 
August 20th. 
" 2:3d, Difr. 

Polynuclear cells, 40.3 per cent. 
Small lymphocytes, 37.6 
Large " 17.0 
Eosinophiles. .5.1 



As the disease progresses the hgemoglobin soon begms to fall, 
later the red cells do so, until, as at tlie end of Case 19 of the pres- 
ent series, the blood may reach the severest grade of anaemia. In 
acute cases the anaemia ma}- develop very rapidly. The usual quali- 
tative changes characterizing severe secondary anaemia may be 
present. 

WJiite Cells, 

AVhen inflammation arises in the glandular tumors and some- 
times when none is found, the white cells may be greatly increased, 
even up to a ratio of 1 : 80 red cells, as in Case 1 of the present 
series, and in the case reported by Vaquez and Ribierre (Soc. INIed. 
d. Hop., 1900, p. 1191), on wdiich between July 24th and August 
27th the leucocytes rose from 35,000 to 51,000 with approxi- 
mately 94 per cent of polynuclear cells throughout. There is, how- 
ever, no more resemblance to leukaemia than in any other form of 
leucocytosis, the polymorphonuclear cells alone being increased. 
There is no reason for supposing, as Eeinert * does, that relative 

' "Die Zahlung der Bhitkorperchen, " Berhn, 1891. 



hodgkin's disease. 181 

diminution of the lymphocytes is owing to the diseased condition 
of the lymph glands, nor for believing with Pinkus (Nothnagel's 
" Specielle Path, nnd Ther.," vol. viii., 1901) that the relative in- 
crecfse of lijm]^jhocytes wdiicli some cases show is characteristic of 
Hodgkin's disease. Pfeiffer^ has recently reported a case of the 
cutaneous form of the disease with 60 per cent of lymphocytes 
out of a total leucocyte count of 6,500. 

As in any other cachectic condition, small numbers of myelo- 
cytes may be found. They were seen in nine of our cases out of 
twenty-iive in which a color analysis was made, the highest per- 
centage being two per cent. Eosinophiles are usually decreased 
when leucocytosis is present. 

Summay'y. 

Xormal blood in early stages. 

Later often marked anaemia; sometimes leucocytosis 

Dlapiostic Value. 

Tlie only help given us by the blood is in excluding leukaemia. 
Syphilis, tuberculosis, or malignant disease might cause similar 
changes or lack of changes in tlie blood. 



Effects of Splexectomy on the Blood. 

When splenectomy is performed for abscess, hydatid, rupture 
of the spleen, or other local disease, it is followed, after a varying 
number of weeks, by a hyperplasia of the lymph glands, associated 
with lymphocytosis. How long this lymphaemia lasts is not alto- 
gether clear. 

Later, after many months, a moderate eosinophilia may appear 
and the mast cells are increased. Ehrlich examined one case six 
months after operation in which a considerable lymphaemia existed, 
the back of the lymphocytes being large. Eosinophiles were not 
increased. In another case he found the lymphaemia persist- 
ing in the fifth year after operation, while the eosinophiles were 
between three and four per cent. In two other cases he found (six 
and eighteen months after the operation) no lymphocytosis. 

iPfeiffer: Wien. klin. Woch., 1897. 



182 



SPECIAL PATHOLOGY OF THE BLOOD. 



In the following table tlie records of four other cases are given : 

Table XI. 









*i"5 


^J 


1 


1 


n^ 


r.'^rr. 




j 


Red cells. 


White 
cells. 


i5 
^1 


Ell 
III 


If 


II 


c 


m 


Remarks. 


*1 


4,570,000 
4,970.000 
5.180.000 
4,800,000 
4,358,000 
3,800.000 


8,000 
30,000 
65,000 
17,500 
11,700 
11.600 


63 
64 

66 

85 
85 


. • 




•• 




.... 


Before operation. 
Three days af t€r. 
Six days 'after. 
Forty-eight days after. 
Four months afti^r. 
Five years after. 


*2 


8,200.000 
4,500.000 


53.000 
18,800 


65 

80 










.... 


(1893. forabsce.ss.) Three 

weeks after. 
Four months after. 


t3 


1,634,000 


12,000 


45 


61 


16 


20 


3 


S.lu 


Operated (April 9th, 1893) 
for malarial hyper- 
trophy with twisted 
pedieie. April 23d. 




2,460,000 


20,000 


87 


49 


18 


32 


1 




May 6th. 




4,580.000 


27,000 


110 


66 


18 


15 


1 


7.7 u 


May 13th. 1894. 




3.977.000 


8,000 


100 


62 


21 


11 


6 




Octo])(>r 2d. 1895. 


H 


4,850.000 


30,000 


108 


83 


8 


8 


1 




Operated for hypertro- 
phied. wandering 
spleen. Before opera- 
tion. 




4,700.000 


39,000 


100 


91 


5 


4 







Seven davs after. 




3,680,000 


18,000 


105 


78 


15 


6 


1 




Two months after. 




2.750.000 


20.000 


63 


84 


5 


10 


1 




Three years after. 



* Czerny : Cited in Laudenbach: Arch, de Physiol., 1896, p. 72i. 
+ Hartman and Vatiuez: Soc. de Biol., February 5th, 1895. 

One point wliich tliese cases clearly prove is that no one variety 
of leucocyte is supplied to the blood from the spleen. 



Splexic Ax.emia. 
(Pseudo-Leukcemia Splenica, Ancemia with Enlarged Sjileen.) 

I object to the term '•'splenic anaemia," because it seems to sug- 
gest that the splenic enlargement is in some way the cause of the 
anaemia, and for this there is no sufficient evidence. But, what- 
ever term is used, there is at least one point about the blood of cases 
of idiopathic anaemia occurring in adults ^ and associated with 
enlarged spleen which deserves notice. This is the leucopeuia. In 

' I do not wish at this point to discuss the significance of similar cases in 
children. See page 519. 



SPLENIC ANJEMIA. 



183 



Osier's article (A?)}. Jour. Med. ScienceSy January, 1900) tlie foL 
lowing counts are recorded : 



1 


Date. 


Red 
cells. 




i-sl 


til 

^11 


ill 


III 


Remarks. 


I. 


Feb. 1879. 


3,250,000 


7,100 








•• 


Recurring hEematemesis and 
melaena. Death In an attack of 
melaena in 1897. 


II. 


1898. 


3,000,000 2,800 


25 


84.4 


12.8 


2.8 


Hasmatemesis for years at inter- 
vals. Splenectomy. Recovery, 


III. 


1898. 


4,000,000 


6,500 


30 


73 


25 


2 


Haematemesis and melaena fre- 
quently. 


IV. 


1895. 


4,816,000 


5,000 


55 










V. 


1896. 


3,600,000 


3,000 


66 


66 


31 


1 




VI. 


1897. 


4,788,000 


5,200 


60 


40 


59 


1 




VII. 


1898. 


4,128.000 


2,800 


45 










VIII. 


1898. 

Jan. 

June. 


3,328,000 2,000 
2,500,000 4,000 


40 
45 


78 


21.5 


.5 


Occasional normoblast. 


IX. 


1899. 


4,208.000 


4,000 


45 


65 


31.2 


3.3 




X. 


1899. 
Oct. 12tli. 

'' 17th. 

Nov. lOth. 
'' 20th. 


1,540,000 

1,380,000 

3,120,000 
3,680,000 


3,300 

3,2.50 

4,500 
4,300 


23 

20 

55 
54 


74 


23.8 


1.5 


Myelocytes, 1.5 per cent. While 
counting 300 leucocytes, saw 
J Normoblasts, 32. 
1 Megaloblasts, 13. 
While counting 400 white cells, 75 
nucleated reds were seen, 21 of 
which were normoblasts, 19 megal- 
oblasts, and 35 intermediate. 

No nucleated reds. 


XI. 


1899. 
Oct. 31st. 
Nov. 16th. 


3,856,000 
3,992,000 


4,500 
3,500 


55 
60 


73.7 


25.3 


1 




XII. 


Nov. 18th. 
1899. 


4,270,000 


2,500 


45 


80.3 


14 


5 


Mast cells, 6 per cent. 



In eight of these twelve cases the leucocytes were markedly sub- 
normal. In some of my cases (see following table) this abnormality 
is still more evident. 

Splenic Anemia. 





Age. 


Sex. 


Red cells. 


White cells. 


Haemoglobin, 
per cent. 


Remarks. 


1 


24 




3,668,000 


15.800 


35 


Polynuclears, 62.0 per cent. 
Lymphocytes, 36.0 " 
Eosiuophiles, .4 " 
Myelocytes. 1.2 " 
:\hist cells, 4.0 « 



184 



SPECIAL PATHOLOGY OF THE BLOOD. 



Splenic An^:mia {Continued). 





Age. 


Sex. 


Red cells. 


White cells. 


Hapmojrlobin, 
per cent. 


Remarks. 


2 


12 




2,268,000 

3,320,000 
3,436,000 


9,800 


25 

22 
25 


With neck glauds. 
Polynuclears, 74.0 
Lvmphocvtes, 25.0 " 
Myelocytes, 1.0 
Normoblasts, = 4.0 (Count 

500. ) 
20 days later. 
56 " 


3 


79 




3,500,000 


9,500 


65 


Diff . count 400 cells. 
Polynuclears, 60.0 per cent. 
Lymphocytes, 35.5 " 
Eosiuophiles, 2.0 " 
Myelocytes, 2.5 


4 


26 




3,634,000 


8,600 


60 


^hirch 9th. 

Polynuclears, 68.0 " 
Lymphocytes. 29.0 
Eosiuophiles, 3.0 








3,968,000 


12,800 


60 


March 19th. 
Polynuclears, 74.0 
Lymphoc3'tes, 25.5 " 
Eosiuophiles, .5 " 


5 


26 




5,216,000 


6,200 


60 


March 7th. 








5,157,000 


4.700 
9,800 


60 


" 9th. 

" 28th. 
Polynuclears, 74.0 " 
Lymphocytes, 24.5 " 
Eosiuophiles, 1.5 " 


6 


36 


. , 


3,300,000 


3,500 


45 


.July 22d. 








3,540,000 


2,800 


35 


•'■^ 26tli. 
Mitral and aortic regurgitation 
compensated. 


7 


13 




4,280,000 


2,100 
1,300 


42 
48 


Polyuuclear, 59. per cent. 
Lymphocytes, 40. " 
Eosiuophiles, 1. " 
No nucleated reds. 
7 days later. 








2,224,000 


6,400 


30 


15 " " dying of hemor- 

rhage. 
Polyuuclear, 55. per cent. 


8 


18 




384,000 


1,800 


35 














Lymphocytes, 37.5 














Eosiuophiles, 7.5 " 














No nucleated reds. 










1,900 


45 


8th day. 








4,024,000 


1,450 
1,500 


35 


12th day. 
15th day. 


9 


45 




3,048,000 


1,600 


35 


Polyuuclear, 44. per cent. 
Lymphocytes, 55. " 
Eosiuophiles, 1. 
Two normoblasts. (Count 
500 cells.) 


10 


17 




2,560,000 


700 


20 


July 21st. 



SPLENIC ANEMIA. 



185 



Splenic Anemia {Continued). 



Age. 


Sex. 


Red ceUs. 


White cells. 








650 








1,700 








900 






2,456,000 


2,' 200 






4,912,000 


1,400 



Htemogloblu, 
per cent. 




Remarks. 



Repeated. Polynucleai', 66^. 
Lymphocytes, 83. per cent. 
Eosinophiles, 1. " 
(No nucleated in 150.) 
July 27th. 
July 31st. 
August 11th. 
August 20th. 

November 18th. Following 
July 5th, doing w^ell. 



Warthin has recently {Traiis. Assn. Am. Fhys., 1903) called 
attention to the fact that in some cases of this type there is stenosis 
with calcification in the portal vein. 

Hocke {Berl. klin. Woch., April 21st, 1902) has reported with 
autopsy a case very similar in all respects to those of Osier (Banti's 
type). The blood showed : 



Red cells. 


Leucocytes. 


Haemoglobin, 


Remarks. 


3,750,000 


3,200 to 5,800; 
near death. 


7 grammes. 


Lymphocytes greatly in- 
creased. 



Yet Hocke considers it congenital lues ! 



PART II. 

ACUTE INFECTIOUS DISEASES. 



CHAPTER III. 

INFLUENCE OF INFECTIOUS FEVERS ON THE BLOOD. 

Some of the blood changes found in acute infections are to be 
regarded as due simply to the fever associated with the disease. 
It is worth while, therefore, to consider what fever ^>^r se can do to 
the blood. 

Maragliano ^ and others have shown that during fever from any 
cause a contraction of the peripheral vessels occurs. When fever 
disappears, whether spontaneously or from the action of antipyretics 
(phenacetin, quinine, etc.), a dilatation of the vessels follows. 

Following the laws to which we have so often alluded, the con- 
traction of the vessels causes a concenti'ation of the blood with rise 
in specific gravity and in the number of blood cells per cubic milli- 
metre. This concentration is still further increased by the greater 
loss of water Avhich the organism suffers during fever than under 
normal conditions. 

The effect of these two influences in increasing the number of 
red cells per cubic millimetre is, however, counteracted to a consid- 
erable extent by the sharing of the blood in the general tissue de- 
struction which goes on with increased rapidity during fever. Many 
corpuscles are thus destroyed, but until the temperature falls the 
anaemia is covered up by the concentration. When the fever leaves 
the patient there is a sharp fall in the number of cells per cubic 
millimetre, due partly to the destruction of corpuscles (hitherto 
masked by concentration) and partly to the dilution of the blood 
which is the result of the post-febrile dilatation of the peripheral 
vessels above mentioned. The suddenness of this fall in the count 
is proportional to the suddenness of the fall in temperature. 

The alkalinity of the blood has been often said to be diminished 
^ Zeit. f. klin. Med., vols. xiv. and xvii. 



PNEUMONIA. 187 

in fever, but' recent research tends to show that these results were 
obtained by faulty technique, and it is doubtful whether the reac- 
tion of the blood shows any constant changes in fever. 

Leucocytes and fibrin show no constant changes, though in the 
majority of infectious fevers they are increased. The tendency of 
the granules of polynuclear cells to lose or change their staining 
affinities in infectious disease has been noted by Ewing, Stengel, and 
Hirschfelt. 

In the active stages of the great majority of infections the poly- 
nuclear cells become increased at the expense of the other forms and 
the eosinophiles become very scarce or disappear. In convalescence 
these changes are reversed, the polynuclears sink, the eosinophiles 
rise above normal, and for two or three months after the fever these 
latter conditions often persist in the blood. 

PNEUMONIA. 

The Blood as a Whole. 

(a) Bacteriology. — The diplococcus lanceolatus has been repeat- 
edly found in the blood of pneumonic patients, especially in those 
in whom there has been some secondary diplococcus infection (e.^., 
diploccoccus endocarditis). 

For example, Sittmann ^ out of 16 cases found diplococci in the 
blood of 6, most of which were complicated with^ lesions in other 
organs, and 4 of which were fatal, while of the 10 whose blood was 
sterile, 9 ended in recovery. 

Boulay ^ found the organism in 2 cases shortly before death. 
Belfanti ^ found it but 6 times out of a large number of cases, and 
of these 6, 5 were fatal. Goldschneider " and Grawitz * got similar 
results. Cohn^ in 32 cases found the organism in 9 ; 7 of these 
were fatal. The other 2 had empyema and other evidences of 
metastatic action of the pneumococci. White (Jour, of Exp. Med., 
1899, p. 425), in his very thorough study of 19 cases, got positive 
results in 3 — all of which proved fatal, as did 7 of the 16 negative 

' Deut. Archiv f. kiln. Med., 1894, p. 323. 
'' Paris Thesis, 1891. 

3 Riforma Medica, Naples, 1890, No. 37. 
''Deut. med. Woch., 1892, No. 414. 
5 Grawitz : Charite-Annak^n, vol. xix. 
«Cohn: Deut. med. Woch., 1897, No. 9, 



188 SPECIAL PATHOLOGY OF THE BLOOD. 

cases. Beco^ studied 49 cases. Twenty of these ended fatally, 
and of these 20 there were 5 whose blood showed pneumococci 
by culture and 1 from which Friedlander's bacillus was cultivated. 
Out of 29 cases ending in recovery only 2 showed cocci in cultures 
from the blood. If large numbers of colonies can l)e cultivated 
from the peripheral blood, Beco considers the prognosis grave. A 
few colonies, however, are of no significance in prognosis. Fraen- 
kel has obtained over 300 colonies from one puncture. Their viru- 
lence was less than that of those in the sputa, showing apparently 
the effects of the blood's antitoxic power. Nevertheless, it is prob- 
able that the presence of pneumococci in the blood is a bad prog- 
nostic sign. The most recent observations made with 5 to 10 c.c. 
of the blood well diluted in luitrient bouillon have shown a larger 
percentage of positive results. Thus Pieraccini ' was successful in 
11 out of 28 cases, and Silvestrini ^ in 15 out of 16, Berghini * and 
Prochaska ' in almost every case, even the most favorable. 

(b) Coagulation is remarkably rapid, and in fresh specimens the 
fibrin network is very tliick and appears within a few minutes, ex- 
cept in the rare cases with subnormal leucocytes. Here it may be 
absent or diminished. 

(c) In cases with cyanosis tlie blood is often concentrated at tlie 
periphery so that its specific gravity is high and the number of cor- 
puscles large. 

(d) Monti and Berggriin ' observed that in children the specific 
gravity was high throughout the course of the disease, falling with 
the temperature. 

The toxicity of the blood is doubled (Albu: Virchow's Archiv, 
vol. cxlix.). 

Hed Cells. 

During the fever the red cells are approximately normal (unless 
increased by cyanosis) ; but after the crisis there is often slight 
anaemia, and sometimes a severe one. The haemoglobin is more 
markedly and more lastingly reduced than the number of red cells. 

1 Beco: Revue de Med., 1899, July 10th. 

2 Pieraccini: Centralbl. f. allg. Path., 1900, vol. xi., p. 470. 
=^ Silvestrini: Centralbl. f. allg. Path., 1900, vol. xi.. p. 447. 
^Berghini: Ref. from Grawitz, p. 516. 

5 Prochaska: Deut. Arch. f. klin. Med., 1901, vol. Ixx., p. 559. 
^ Arch. f. Kiuderheilk., vol. xvii. 



PNEUMONIA. 



189 



A more interesting and important observation was made by 
Tiirck in 1898, viz., tliat when the infection is severe or the patient 
of low vitality nucleated red cells (mostly normoblasts) may appear 
in the peripheral blood. In all Tiirck 's cases megaloblasts as well 
as normoblasts occurred, but the latter were greatly in the majority. 
Dr. Badger and I studied a most interesting case of this type in 
1898. The pneumonia ran a severe course and was followed by an 
empyema which proved fatal. The blood counts were made for the 
most part after the crisis. At autopsy the marrow of the femur 
was bright red from end to end. The blood showed the following : 



Date. 


Red 

cells. 


White 
cells. 


2 d"53 
So J, 


^11 


III 


III 

111 


6 M'fl 


111 

a.-§ s 


|l 


a 


1898- 

JanuarylSth 

14th 

15th 

16th 

ITth 

18th 

19th 

30th 

21st 

22d 

34th 

36th 


4,52b',666 


61,000 
71,500 
59,000 
51,800 
47,000 
26,700 
19,700 
25,000 
24,000 

14.406 
19,100 


ii 


) 


9b'6 

84.5 
84.5 
86.6 
87.3 

92.5 
92.0 
87.0 


■ v. 6 

8.0 
12.8 

6.1 
10.0 

■ 7.5 
7.6 

12.5 


*d.2 

0.8 
0.25 


3.0 
7.5 
2.5 
6.5 
3.5 

0.3 
0.25 


"eoo 

600 
600 
700 
500 

*466 

300 
400 


23 
93 
54 
24 

? 

*3 
3 


'4 

15 
4 
3 

? 

i 



Many of Ttirck's stimulation forms and many neutrophlles intermediate between myelo- 
cytes and polynuclear cells were seen. 

Maragliano has noticed " degenerative " changes in the red cells 
in severe cases. 

Wh ite Coiyuscles . 

1. Probably as early as the time of the chill, and certainly within 
a few hours after it, the leucocytes are greatly increased, and usu- 
ally continue so throughout the febrile period. 

2. There is no correspondence between the daily variations in 
temperature and the leucocyte curve. In cases in which a pseudo- 
crisis occurs (the temperature falling but rising again), the leuco- 
cyte count usually remains high, while at the time of the true crisis 
and often a few hours before it the leucocytes begin to fall. This 
fall, however, is hardly ever by "crisis," but though starting perhaps 
a little before the temperature, it is one to two days longer in reach- 
ing normal. When the temperature reaches normal by Ij^sis the 
leucocytes fall with it, but generally more slowly, and reach normal 
later. 



190 SPECIAL PATHOLOGY OF THE BLOOD. 

3. AVhen resolution is delayed the leucocytosis continues, some- 
times for weeks, and very gradually falls to normal in cases in 
which resolution eventually occurs without complication. If ab- 
scess, empyema, or gangrene follow, the leucocytes usually become 
still further increased. 

4. The degree of leucocytosis is })robably the resultant of the 
factors mentioned on page 97, and does not run parallel to the de- 
gree of fever or the amount of lung involved. Nevertheless, cases 
with extensive signs in both lungs, and especially those complicated 
by empyema or other suppuration, are more apt to have very high 
counts, provided the " reaction " of the patient against the infection 
is vigorous. Children have especially high count as a rule (see ex- 
ception below). The cases appear to fall into the following groups 
as regards the degree of leucocytosis present: 

1. Mild infection, vigorous reaction — slight leucocytosis. 

2. Severe or moderate infection, vigorous reaction = marked 
leucocytosis. 

3. Severe infection, feeble reaction = no leucocytosis. 

(a) The patients in Class 1 all recover, but they are very few in 
number, (li) Those in Class 2, which includes over nine- tenths of 
all cases, may or may not recover, according as the fight between 
patient and disease comes out one way or the other. 

(c) Those in Class 3 almost invariably die : there is not sufficient 
of a struggle to raise the leucocyte count. A striking exception to 
this rule is reported by Stockton {Fhil. Med. Jour., June 25th, 
1898), a case of lobar pneumonia in a child of eight with three 
relapses and a total course of sixty-eight days. At the height of the 
second relapse the blood was examined and showed only 4,000 
leucocytes per cubic millimetre. Of these there were 44 per cent of 
polymorphonuclear, 50 per cent small Ij'uiphocytes, 6 per cent large 
lymphocytes. In the second apyretic interval, sixteen daj'S after 
the first examination, the count stood 7,840 leucocytes per cubic 
millimetre. Of these, 34 per cent were polymorphonuclear, 60 per 
cent small lymphocytes, and 20 per cent eosinophiles, 4 j^er cent 
large lymphocytes (?). 

After the third seizure (three weeks later) the leucocytes were 
10,080, with polymorphonuclear 45 per cent. Small lymphocytes 
46 per cent, eosinophiles 8 per cent, large lymphocytes 1 per 
cent. 

On the sixty-eighth day (in convalescence) the blood showed : 



PNEUMONIA. 191 

Eed cells, 4,952,000; white cells, 7,600; hsemoglobin, 90 ])ev cent. 
Polymorphonuclear, 57; small lymphocytes, 36; large lymphocytes, 
2.5; eosinophiles, 4.5. 

Yery possibly this infection may have been due to some other 
organism than the diplococcus lanceolatus. 

When either the patient or his disease easily gains the mastery 
there is no leucocytosis, or a very slight one; but in the much larger 
class of cases in which the struggle is a fierce one, leucocytosis ap- 
pears, whichever way the struggle results. 

Pick 1 noted that pneumonia complicating smallpox when the 
patients were already very sick, caused no leucocytosis, and the same 
is often true in those whose power of resistance is reduced by age, 
alcoholism, typhoid, or by some chronic disease. 

Von Jaksch, noticing the fatality of cases without leucocytosis, 
suggested that we should induce leucocytosis by injecting turpen- 
tine or other irritants so as to cause abscess; but this has not proved 
of any benefit to the patient, nor has the production of leucocytosis 
without abscess, as can be done with pilocarpine or nucleiii, been 
any more successful. There is no difficulty in producing the leuco- 
cytosis by these means, but all observers are agreed that it does the 
patients no good. 

Leucocytosis is checked by antipyretics (Hare ^) but not by cold 
bathing, which speaks in favor of the latter method of reducing 
temperature. 

The general course of the leucocytes is seen in the accompanying 
charts from Billings, to whose excellent article I am greatly in- 
debted. 

Qualitative Changes. — As in most forms of leucocytosis, the 
polymorphonuclear leucocytes are enormously increased both abso- 
lutely and relatively, often making over eighty per cent of all the 
white cells. ^ Eosinophiles and blood plates disappear and the 
lymphocytes are absolutely and relatively much reduced. After 
the crisis this is reversed, the polymorphonuclear forms falling 
often below sixty per cent, while the eosinophiles and blood plates 
are above normal. The return of the eosinophiles to the circulation 

' Arch. f. Dermat. und Syph., vol. xxv., p. 63. 

2 New York Medical Record, May 9tli, 1896. 

'Loper believes that if the polynuclear cells make up from ninety to 
ninety -five per cent of all the leucocytes, the prognosis is very bad (Arch, de 
med. exp., 1899, p. 724). 



192 



SPECIAL PATHOLOGY OF THE l^LOOD. 



often occurs a day or two before the crisis. It seems to mean that 
the acme of the process has passed, and so constitutes a favorable 

Chart I. — Pneumonia, Shoaving Fall by Crisis (Billings). 



Feh. 1 


16 1 17 


18 


p / 


? 


1 

S r 


.9 


20 \ 21 \ 


22 


1 
f 7 


1060 
































































































,(K'r> 
































































t 
































i(yr 








•^ 








» ' 










































\ 






/ 
































103° 












'1 






\ 














































































102° 






























































\\ 






k 




























101" 














I 








^ 
















































I 


























100° 














































































^ 


















99° 


































/ 














98° 






... 


... 












- 


-- 


v 


-' 






w 










•~ 


.. 


... 


































































80,000 
40,000 
90.000 

ao.000 

18.000 
J6.000 

lajm 

B.00O 
»,000 
8.000 

4.000 
3.000 
































































































































































































• 














































\ 














































' 






























































































i 














































\ 














































\ 






^ 








































\ 








S, 










































f 




















































Vi 




^ 


































\l 














































X 














\ 














































\ 














































\ 














































































































































\ 
















































y 
















































s 














... 


































V ^ - - 






































































































-i-. 


_ 




_ 




_ 
















_ 


_ 


_ 




1 






_ 


_ 



The npper chart shows the course of the temperature, the lower that of the 

leucocj'tes. 

sign in most cases. After the crisis the eosinophiles may run up to 
five to six per cent (300-450 absolute). 

Myelocytes may be abundant (11.9 per cent or 1,056 absolute) 
and stimulation forms and transitional neutrophiles numerous. 
They have no known prognostic significance. 

At and just after the crisis a great increase of blood plates takes 
place, gradually disappearing later. 



PNEUMONIA. 



193 



As to the differential count in the (fatal) cases in which leuco- 
cytosis is absent, data are scanty. Bieganski thought the polymor- 
phonuclear varieties decreased, Eieder found them increased, while 
Billmgs found them normal. No general law can be stated on this 
point as yet.^ 

In a case of bronchopneumonia complicating pertussis studied at 
the Massachusetts General Hospital in 1894, the conditions were 
entirely different from those just stated. The patient, a girl of six, 
had at entrance 72,100 leucocytes per cubic millimetre. Two days 



Chart II. — Pneumonia and Rheumatism. 



2^ 


f. i& 


26 


May 


9 


?9 


3ff 


5/ 


, 


2 3 


ine. 

4- 


^ 


6 




/OS" 




































































105" 




































yt 
































I04!> - 


































^ 


































/a?" 




































\ 
































/oa" 


\ 


































i« 
































Wl'> 




V 


































. 






























100° 


















1 












1 






































99" 












\ / 






^ ^ i- 




X^ 




V 




J 




93" - 







.._.. 


.... 


- 


.v:_ 


' V * 


i. ... 




iJ)l 




V 


• V 


Ht 


r 






































97° 




































































W.00O 
















p 


































<j 


_^ 
































'< 


i 


















^ 














3 


^ 


















/ \ 














<= 


















80.000 


/ 


>^ 












"" 




K 














18,000 _j 




, 












r 


" 


' \ 














16,000 i 




H 






























14,000 












A 




/ 






\ 








• 




18.fl0O 




s 


\ 




/ 














V- 










10.000 








^ 






^J 
















" 




8.00O 






W-- 








U 


















- 


6,000 


































4,000 _ 


































a,ooo- 






































■ »• 








. 




- 



















The upper chart shows the course of the temperature, the lower that of the 

leucocytes. 

after the count was 94,600. A differential count made at the same 
time showed that the small lymphocytes made up 66 per cent of all 

^ lodoiildUa is present and marked in practically all cases. Dunn has noted 
that while in cases ending with crisis and resolution the reaction disappears 
in a day or two, it persists in those with delayed resolution. 
13 



194 SPECIAL PATHOLOGY OF THE BLOOD. 

the 94,600 leucocytes per cubic millinietie. The pulymorphonucleai- 
cells were reduced to 30 per cent. Lympliatic leukaemia was thought 
of, but the leucocytosis was gone in ten days, and within a fort- 
night the patient left the hospital well. In the light of recent 
studies in pertussis this is now explicable (see page 220).^ 

Diagnostic and Prognostic Value. 

1. In cases of so-called " central pneumonia " in which the symp- 
toms but not the physical signs of the disease are manifest, the 
presence of a well-marked leucocytosis is often of great diagnostic 
value. It excludes malaria, typhoid, and uncomplicated grippe as 
causes of fever, and if scarlet fever and suppuration can be excluded 
by other evidence, it makes pneumonia very probable. 

I have repeatedly seen the diagnosis of pneumonia made in the 
absence of physical signs and largely on tlie evidence of the blood 
count, the diagnosis being confirmed several days later by the ajj- 
pearance of typical signs of consolidation. In a patient of Dr. F. 
C. Shattuck's, sick five days, yet showing no signs of consolidation 
of the lung, the presence of a marked leucocytosis excluded typhoid, 
the only other likely diagnosis, and led Dr. Shattuck to treat the 
case as pneumonia, the wisdom of which course was later demon- 
strated by the appearance of signs of consolidation. 

2. Between pneumonia and capillary bronchitis the condition of 
the blood is of no help, as the latter also causes leucocytosis, and 
some cases affecting the larger tubes do the same. 

3. In cases of pneumonia occurring in very old or very young 
people, in which the fever and symptoms may be very slight, the 
presence of leucocytosis may be the first thing to direct our atten- 
tion to the lungs, dyspnoea and cough being absent. 

In prognosis, the important point is that the absence of leucocytosis 
is a very had sign, while its presence is neither good nor bad. It 
must be remembered also that in the very mildest cases we may find 
the same absence of leucocytosis which in any other but the mildest 
would be almost surely fatal. 

This last point, which appears to me of great importance, is 
illustrated by the following figures : 

Halla reported 14 cases; 2 had no leucocytosis, and both were 
fatal. 

' Stienon: Jour, de Med., de Chirurg. et de Pharm., Bruxelles, 1895, t. iv., 
fasc. 1. 



PNEUMONIA. 195 

Billings reported 22 cases; 1 had no leucocytosis and was fatal. 

Laelu' with 16 cases, and Rieder with 26, got similar results. 

Ewing in 101 cases found leucocytosis absent in 6; 6 were fatal. 

Yon Jaksch and Kilodse likewise maintain that the absence of 
leucocytosis is usually fatal. 

In our series 812 cases have been studied. In general they 
entirely confirm the results obtained by Billings and summarized 
above : 90 of them presented no leucocytosis at any time, and of 
these 83 were fatal; another one seemed moribund but finally re- 
covered. 

The evidence, therefore, is in favor of the view that when leuco- 
cytosis is persistently absent in any but the mildest cases the prog- 
nosis is almost fatal. The 'presence of leucocytosis, on the other hand, 
Is no guaranty ichatever of a favorable issue. 

Reappearance of eosinophiles is a favorable sign in most cases. 
Indeed Becker {Devt. med. Worh., 1900, p. 558) states that he has 
never found eosinophiles in fatal cases. The counts at the time of 
entering the hospital may be summarized as follows : 

Cases with leucocytes under 10,000 = 90 
" " " between 



00 = 90 


(83 of these fatal) 


10,000 to 


15,000 = 125 


15,000 " 


20,000 = 192 


20,000 " 


25,000 = 186 


25,000 " 


30,000 = 114 


30,000 " 


35,000= 47 


35,000 " 


40,000= 44 


40,000 " 


45,000= 20 


45,000 " 


50,000= 10 


50,000 " 


55,000 = 7 


55,000 " 


60,000 = 2 


60,000 " 


65,000 = 3 


65,000 " 


70,000 = 1 


LOO, 000 " 


110,000 = 1 



842 
Bronchopneumonia, 

In sixty-eight cases of bronchopneumonia recorded at the Mas- 
sachusetts General Hospital, the following counts are recorded : 

Counts. 

Between 5,000 and 10,000 = 10 

10,000 •' 15,000 = 18 

" 15,000 '• 20,000 = 25 

" 20,000 " 2r>.0()0 = 24 



196 SPECIAL PATHOLOGY OF THE BLOOD, 





Counts. 


Between 25,000 " 


30,000= 9 


30,000 •■ 


35,000= 8 


35,000 ^• 


40,000= 1 


40,000 •' 


45,000= 2 


45,000 " 


50,000= 2 


50,000 " 


55,000= 1 


" 100,000 " 


185.000 = 3 (same case) 




103 



The liighest counts in this series were in a case of broncho- 
pneumonia in a baby of fifteen months. As the lymphocytes made 
up the larger part of the increase, and as the cough came in parox- 
ysms with great cyanosis, pertussis was suspected. This case has 
already been referred to on page 106, and a similar case is recorded 
on page 193. 

TYPHOID FEVER. 

Bfirtt^riohK/)/ of tJic BJood. 

Although it has long been known that the bacilli of Eberth 
could occasionally be found in tlie circulating blood or in the rose 
spots of typhoid cases, yet it is only within the last few years that 
such findings have been sufficiently constant to be of an}* practical 
value in diagnosis. The earlier investigators found the organism 
but seldom, probably because they used too small quantities l^oth of 
blood and of nutrient bouillon. Using a larger amount of blood 
and diluting it well, it seems that bacilli can be found in the blood, 
of most cases. Thus Busquet (Presse 2Ied., June 21st, 1902) found 
them in all of 43 cases, generall}' at first examination. 

Schottmuller (3Iunch. med. WocJi., September 23d, 1902) was 
successful in 182 out of 220 cases (82 per cent), occasionally in the 
first twenty-four hours, often by the fifth day, alwaj'S in the second 
or third week. The bacilli were not found after normal temperature, 
but returned in relapse and recrudescence. 

]S"eufelt,i Curschmann,^ Scholz and Krause,^ and Eichardson* 
have succeeded in cultivating the bacilli from the rose spots in a 
total of 46 out of 56 cases. 

^Neufelt: Zeit. f. Hyg., xxx., 3, p. 499. 

^Curschmann: Miinch. med. Wocli., 1899, p. 1597. 

3 Scholz aud Krause: Zeit. f. kiin. Med.. 1900, vol. xli., p. 405. 

^Richardson: Phil. ^Icd. .Torn-., March 3d. 1900. 



i 






TYPHOID FEVER. 197 

Quantitative Changes. 

1. The hlood plates are usually scanty, and the amount oi fibrin 
is diminished. In one of Tiirck's cases, blood plates and fibrin 
were nearly absent, and a hemorrhagic diathesis developed. He 
considers a rapid falling off of the amount of fibrin and blood plates 
a bad prognostic sign, but in a case of hemorrhagic typhoid reported 
by Hamburger (Johns Hopkins Hospital Keports, vol. viii.) recovery 
took place, although the coagulation time was ten minutes. 

2. Specific gravity follows the course of the haemoglobin. 

3. The general effects of fever (see page 186) are in part ac- 
countable for the changes next to be described, while some of them 
are more peculiar to typhoid fever. 

Red Cells, 
In Thayer's admirable study (Johns Hopkins Hospital Keports, 
vol. viii.) we find the following analysis of two hundred and sixty- 
five counts : 

Weekly Average Based on One Count per Week in Each Case, the 

Average Being Taken for the Week in Every Case in which 

Multiple Counts Were Made. 

1st week 32 counts 4,913,312 

2d " 83 " 4,706,855 

3d " 54 " 4,555,814 

4th " 34 " 4,187,720 

5th " 22 " 4,118,590 

6th " 87 " 4,028,428 

7th " 8 " 3,309,125 

8th " 8 " 3,652,285 

9th " 6 " 3,509,666 

10th " 1 couDt 3,920,000 

11th " 1 " 2,109,333 

All these counts refer to the febrile period of the disease. 
Eighty counts were made during convalescence. The results 
were as follows : 

Estimates of the Red Blood Corpuscles During Convalescence 
Arranged According to the Period after the Last Day of Fever. 

1st week, 32 counts 4,540,000 

2d " 22 " 4,637,100 

3d " 15 " 4,252,000 

4th " 6 " 4,391,000 

5th " 2 " 5,469,000 



198 SPECIAL PATHOLOGY OF THE BLOOD. 

Thayer conmients : " It will be noticed that in the first week (of 
fever) the number of red blood corpuscles is already somewhat be- 
low the normal" — that is, taking the normal as from 5,500,000 to 
6,000,000, as it seems proper to do in this country (see page 54;. 

From tliis point it steadily sinks week by week for the first nine 
weeks. After that the number of counts is too small to justify (-(tn- 
clusions. Tlie lowest point is probably reached about the end of 
defervescence in the majority of uncomplicated cases, yet when def- 
ervescence is slow, blood regeneration may begin well before tlie 
end of the febrile period. In the first two weeks of convalescence, 
regeneration is going on slowly. "After the second week, in addi- 
tion to the fact that the estimates are but few, the results are viti- 
ated by the fact that the cases remaining in the hospital at so late 
a period were for the most part instances of severe fever of long 
duration, after which, as is shown by the first table, a much greater 
degree of ansemia is reached" (Thayer). 

Showing the Highest and Lowest Coints ix Each Week. 

Highest. Lowest. 

1st week 6.U40.000 3.400,000 

2d " 6.604.000 2,240,000 

3d " 6.916.000 2,300.000 

4th " 5,884.000 1,426,000 

5th " 6,312.000 1,352,000 

6th " 4,904,000 2,014,000 

7th " 4.500. UOO 1.648,666 

In only one of these cases could the high count be explained as 
a concentration of the blood through diarrhoea and vomiting, but 
counts made just after a bath are often very higli owing to blood 
concentration. 

Hmmoglohin. 

Thayer's figures are as follows: 

1st week of fever, 21 estimates average 76 per cent. 



2d " 


50 


3d " 


32 


4th " 


20 


5th " 


15 


6th " 


6 


7th " 


4 



60 
58 
62 
50 



Convalescence 1st week, 22 estimates average 67 per cent. 

" 2d "19 " " ^ 69 

3d ■12 " " 67 



TYPHOID FEVER. 199 

This table shows a gradual decline during the febrile period, 
with a very slow regeneration in convalescence. The haemoglobin 
(as in most secondary anaemias) suffers more than the count of cor- 
puscles, and is slower in reaching the normal, so that the color in- 
dex is low throughout (see chart on page 201). 

Leucocytes. 

Thayer records 832 estimates of the white cells in uncompli- 
cated cases. 

Based od one count per week in each case, the average being taken for 
the week in every case in which multiple counts were made. 

1st week of fever, 100 counts 6,400 

2d " " 206 " 6,200 

3d " '• 150 " 5,700 

4th " " 95 " 5,400 

5th " " 58 " 5,380 

6th " " 19 " 5,800 

7th " " 13 " 6,300 

Sth •• " 12 " 6.400 

Thayer comments : " It would seem that the longer the disease 
lasts, the more profound the prostration, tlie lower the count." 
Ewiug sa^^s: "The more severe the t3'phoid intoxication the lower 
the count.'' How great the variations ma}' be even in the absence 
of any apparent complication is shown in the following table : 



1st week of fever 15,000 

2d 



3d 

4th 

5th 

6th 

7th 

8th 

9th 



Highest. 


Lowest 


15,000 


1,600 


18,000 


1,000 


13,000 


1,000 


10,500 


1,700 


10,500 


2,300 


10,000 


3,250 


11,000 


4,000 


9,250 


4,000 


9.300 


2,000 



Most of these high counts were in the blood of one individual, 
who, throughout the disease, without any apparent reason, showed 
constantly a large number of colorless corpuscles. The count of 
18,000 may have been after a cold batli, which Thayer has previ- 
ously shown often raises the count of white cells. 



200 SPECIAL PATHOLOGY OF THE BLOOD. 

In convalescence the count of leucocytes begins to rise toward 
the normal as the following table indicates : 

1st week of apyrexia, 32 counts 6,000 

2d " •' 24 •' 6,700 

3d " •• 16 " 6,300 

4tli " " 6 " 7,570 

Thayer's results may V)e exhibited in the chart on the following 
page. 

In the majority of the l,oo7 cases recorded at the Massachu- 
setts General Hospital, the course of the leucocytes from week to 
week has unfortunately not been followed with accuracy. 

Most of our counts were made on the day of entrance to the hos- 
pital, presumably during the first or second week of the fever. 

The range of the counts was as follows : 

13 cases. 



Bet weeu 1,000 and 2,000= 13 


2,000 '• 


3,000= 62 


• 3,000 " 


4,000 = 171 


•• 4,000 " 


5.000 = 230 


" 5,000 •' 


6,000 = 224 


•' 6,000 " 


7,000 = 217 


" 7,000 " 


8,000 = 150 


" 8,000 " 


9,000 = 118 


" 9,000 '^ 


10,000= 81 


" 10,000 •' 


11,000= 43 


" 11,000 " 


12,000= 27 


" 12,000 " 


13,000= 12 


" 13,000 " 


14,000 = 6 


" 14,000 ■• 


15,000 = 3 



1,357 •' 

From these figures I have excluded all cases counted only under 
circumstances likely to concentrate the blood (c}-anosis, after baths, 
after severe diarrhoea). 

Of these cases 1,309, or 97 per cent, had less than 11,000 leuco- 
cytes per cubic millimetre at the time of entering the hospital, and 
77 per cent had less than 7,000. 

But these figures, like those reported by Thayer and Ttirck, 
differ from the reports of some other observers in not showing so 
large a proportion of very low counts. Thus Khetajurow expects 
to find only 2,500 to 3,000 leucocytes in the third and fourth weeks, 
but our observations show that this is not a law. 



TYPHOID FEVER. 



201 



Complwations. 
Thayer's study of tlie effects of complications is by far the most 
thoiough ever published. 

Chart of the Blood in Typhoid Fever. 
Febrile period — weeks. Convalescence — weeks. 



/J?3^S<!T^f> / i 1 


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yV^/7 






































































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Plain line = red cells. Dotted line = haemoglobin. Broken line = white cells. 

1. Hemorrhcuje from the Boicels (11 cases). The red cells fall 
off markedly in one case from 3.648.000 (eighteen days before) to 



202 SPECIAL PATHOLOGY OF THE BLOOD. 

1,992,000, ill another to 2,000,000; yet the lirst of these (•a>e> 
recovered. 

The leucocytes showed uo appreciable change in half of these 
cases, while in the rest there was some leucocytosis (24,800 in one 
case, 17,400 in another, 10,500 in a third), reaching its maximum 
in from twelve to twenty-four hours, and returning to normal in 
from two to seven days. 

2. Perforation of the Bowel (8 cases). Leucocytosis was well 
marked in three (16,400, 23,400, and 16,000), slight in two 
(10,400 and 11,200), and completely absent in three, at the time of 
the perforation. Thayer studied the clinical features of these cases 
and the results of cultures made at operation, and concludes: "It 
is probable that slight local peritonitis always produces . . . leuco- 
cytosis unless the individual is already in a condition of profound 
general septicaemia. On the other hand, a sudden (general) infec- 
tion of the peritoneum with large quantities of excessively malig- 
nant organisms may often result in complete absence of leucocytosis 
or a relatively slight rise, followed later by a fall. Three cases of 
streptococcus peritonitis showed no leucocj'tosis at any time. The 
prospect of relief by surgical interference is best in those cases with 
a leucocytosis.'" Thayer also shows that a preperforative leucocy- 
tosis due to local peritonitis about deep ulcers may occur. He adds, 
however, a summary of four cases in which symptoms suggesting 
perforation and accompanied by leucocytosis led to a laparotomy, 
yet in which no perforation was found, the symptoms being due in 
one case to thrombosis of the left iliac vein, while in the others no 
cause was found. In many of these cases the leucocytosis was very 
transitory, and without frequent (almost hourly) counts would have 
been overlooked. 

In the series of cases of typhoid perforation reported b}- Shat- 
tuck, Warren, and Cobb {Boston Medical and Surgical JournoK 
June 28th, 1900) there are four cases of general peritonitis with no 
leucocytosis (3,800, 5,400, 7,300, and 8,000), and four cases with 
leucocytosis (14,000, 16,000, 17,200, and 23,000). Two cases with 
leucocytosis (14,300 and 13,200) showed at operation a perforation 
protected by local adhesions. In most of these only one count is 
recorded, «so that the observations are of little value. 

There is no doubt that leucocytosis does occasionally occur when 
no complication exists so far as ice can asceHain during life. Four 
of the cases over 11,000 (see the above table) were counted repeat- 



TYPHOID FEVER. 203 

edly and complications were carefully sought for, but none were 
found. The most striking case showed the following counts : 

October 3d 13,100 

4tli 13,000 

5rb 16,500 

Ttli 13.300 

8tli 11,200 

" 10th 10,600 

" 13th 13,500 

" 15tli 17,700 

" 17tli 15,500, death ; autopsy. 

The autopsy showed typical typhoid lesions and nothing else.' 
Another and much milder case showed 11,000-12,000 white cells 
constantly for over two weeks, and no cause could be found to ac- 
count for it. 

In typTiokl septicaemia with endocarditis but without intestinal 
lesions, Mayet and Bertrand {Soc. Med. d. Bop., 1900, p. 996) 
report : 

October 19th 13,800 with 91 per cent, of polynuclears. 

21st 14,800 " 93 

" 23d 10,000 " 91 

■" 27th 18,900 " 94 " 

The typhoid bacillus was obtained in pure culture from the blood. 

?^. Furnnculosis. — Thayer records 7 cases in all, of which the 
leucocyte count is very slightly raised ichen ive compare it with that 
vsiudly found in tijphokl {e.g., 9,000, 10,000, 10,200, 10,600, etc.). 

4. Thrornhosis — six cases in Thayer's study are of especial in- 
terest, because the leucocytosis with which each was associated ap- 
peared in three cases earlier than any of the localizing symptoms, 
such as pain and oedema. 

The counts varied from 8,000 and 21,000 in femoral phlebitis 
to 24,800 in plugging of the iliac vein. I have had two similar 
cases. 

o. Fleurisy — 5 cases, all showed slight leucocytosis (10,000- 
12,000). Only in the purulent cases (empyema) was the count 
higher (23,000, 18,000). In one case the tapping revealed a bloody 
and purulent fluid containing only typhoid bacilli. After the tap- 
ping the leucocytes rose to 44,500. 

In most of these cases the percentages of the different varieties 

^ Thrombosis of internal veins and osteomyelitis were not carefully searched 
for at autopsy and may have existed. 



204 SPECIAL PATHOLOGY OF THE BLOOD. 

of leucocytes was but little affected {('(j , 68 per cent of polynuclear 
cells and 1.8 per cent of eosinophiles with a count of 2.3,000 leuco- 
cytes). This is not an ordinary leucocytosis 

6. Piieiinionia — 5 cases, 3 with leucocytosis, 2 without it (ter- 
minal infections). Both of those without leucocytosis and 2 of the 
others proved fatal. The counts were 35,000, 38,000, 8,200, 4,000 
and 6,000. The neutrophiles were not increased as much as in 
ordinary leucocytosis. Ttirck records a case with but 1,600 leuco- 
cytes despite lobar pneumonia, and Kohler mentions several similar 
cases. 

Bronchitis (severe') and BronclLOjjneunionia — 4 cases, 3 showed 
leucocytosis (16,600, 17,200, 18,200). 

8. Periostitis — 3 cases with leucocytosis reaching 22,000, 17,600, 
and 13,000 (only 72 per cent of polynuclear cells in first case). 

9. Suh in axillary Abscess (streptococcus) with a nuiximum count 
of 18,200 which develoj)ed late in the course of the process. In 
another case with perforation peritonitis, the submaxillary abscess 
(staphylococcus and typhoid bacillus) did not produce any rise in 
the leucocytes. 

10. Otitis Media — 2 cases with leucocytosis of 15,600 and 11,800 
(maximal). I have had 10 cases with maximal counts of 16,400, 
14,000, 11,200. 

11. Parotitis — 3 cases, no leucocytosis in 2; in the other 30,500 
(general infection with the staphylococcus aureus found at autopsy). 

12. Perirectal Abscess — 25,100 leucocytes. In one of my cases 
(moribund) a large ischio-rectal abscess developed without produc- 
ing any leucoc^^tosis. 

13. Pericarditis (dry) — 11,500 leucocytes. 

14. Bed-sores (3) — 16,000 leucocytes (average). 

15. Conjunctivitis — 9,330 leucocytes (polynuclear cells 74 per 
cent) . 

16. Cholecystitis — 3 cases, all showing leucocytosis; 28,500, 
21,200, and 14,400 (maximal). 

17. Cystitis — 3 cases, 1 with marked leucocytosis; 18,000. 

18. Urethritis — 3 cases, 1 with 13,700 leucocytes, of which o.o 
per cent were eosinophiles. 

19. Tuberculosis (pulmonary) — 1 case with 14,200 leucocj^tes, 
of which only 55 per cent were polynuclear. Tlirck records a simi- 
lar case with a normal leucocyte count. Pregnancy and peripheral 
neuritis seemed to have no especial effect on the blood. 



TYPHOID FEVER. 



205 



Qualitative Changes. 

Red CoTjmsclcs. — Ttirck notes "the relatively frequent presence 
of marked differences in the size of the red cells with very numer- 
ous dwarf forms; occasionally poikilocytosis and polychromato- 
philia," i.e.^ the changes common to all varieties of secondary 
anaemia. 

White CeUs. — Thayer's extensive and painstaking studies are 
exhibited in the following table : 

Table XII. 







Polymorpho- 


Small 


Large 








nuclear 


mono- 


mono- 


EoslnopWles, 




Counts. 


neutrophlles, 


nuclear. 


nuclear. 


per cent. 






per cent. 


per cent. 


per cent. 




First week of fever 


12 


74 


13 


12 


0.5 


Second " " .... 


39 


71 


14 


13 


0.8 


Third " " .... 


34 


66 


21 


11 


0.3 


Fourth " " .... 


19 


65 


20 


14 


0.4 


Fifth " " .... 


8 


62 


18 


19 


0.3 


Sixth " " .... 


4 


58 


22 


13 


6.0! 


First week apyrexia . . . 


12 


61 


21 


15 


3.0 


Second " " 


7 


49 


31 


17 


2.3 


Third " 


6 


57 


15 


23 


3.5 



These averages, however, cover up some aberrant percentages. 
For example, there was one case which in the first week showed 
15,000 leucocytes, of which 92,3 per cent were polymorphonuclear 
neutrophiles. No complication could be found. The lymphocytes 
were but 7.7 per cent, and the eosinophiles had altogether disap- 
peared. Nine days after defervescence the leucocytes were 9,000, 
with 48.3 per cent of neutrophiles, 43.1 per cent lymphocytes, 
while the eosinophiles had risen to 8.6 per cent. 

High percentages of polymorphonuclear neutrophiles sometimes 
occurred without an increase in the total count, e.g., in the second 
week a case with 8,000 leucocytes, of which 94 4 per cent were 
polymoiijhonuclear, and in the third week a case with 4,000 leuco- 
cytes, of which 82 per cent were polymorphonuclear 

In the ninth week one case showed 12,7 per cent of eosinophiles 
with 70.4 per cent of polymorphonuclear neutrophiles. 

Summing up Thayer's observations, we find: 

1. A steady diminution in the polymorphonuclears, the lowest 



206 SPECIAL PATHOLOGY OF THE BLOOD. 

point being reached at the end of the pyrexia. This is an absolute 
diminution, 

2 A relative increase in the lymphocytes, especially the larger 
forms; absolutely their number is not much changed. 

3 A reduction (relative and absolute) of the eosinophilic cells 
during the pyrexia followed by an inci-ease in convalescence, wliich 
may amount to a considerable eosinophilia. 

Ttirck's results are practically the same. He adds that eosino- 
philes may actually disappear from the blood at the height of tlie 
disease, and considers that their reappearance or increase previous 
to defervescence augurs a relatively short course for the fever, and 
(aside from the occurrence of complications) a good prognosis. 
Myelocytes and Beiztiagsformen were occasionally present in his 
preparations, even in a case with a leucopenia of 4,200 and but 52 
per cent of polymorphonuclear neutrophiles. 

Xaegeli (Deict. Arch. f. klin. Med., vol. Ixvii., p. 279) lias 
made a most careful study of fift}^ cases with fifteen to twenty 
observations in each. His conclusions are: 

I. In the first week, during the " step-ladder " ascent of fever, 
there may be a slight polynuclear leucocytosis. 

II. The second and third weeks are characterized by leucopenia, 
with a marked diminution of pol3'nuclears, slight diminution of 
lymphocytes, and ahseuce of eosinophUes. 

III. In the "period of steep curves " eosinophiles reappear, lym- 
phocytes increase. 

IV. Convalescence : Polynuclears reach their minimum while 
lymphocytes and eosinophiles rise above normal. It takes about 
two months for the blood to return to normal. All these changes 
are more marked in children. Naegeli considers the eosinophiles 
of importance in prognosis, and considers that in complications 
the polynuclears should rise. If they do not the prognosis is poor. 

Kolner {Deut. Arch. f. Jclln. Med., 1898, vol. xl., p. 221) found 
that in cases complicated by pneumonia or otitis, the leucocytes 
were sometimes increased and sometimes diminished. 

lodophilia occurs in a small proportion of the polynuclear cells 
at some time during the course of most cases of typhoid fever, espe- 
cially on the second and third weeks. 



TYPHOID FEVER. 207 



Suvimary. 

1. The red cells suffer to the extent of about 1,000,000 in the 
course of an average case, the reduction taking place gradually, 
and being most marked at the end of defervescence in most cases 
Sweating, vomiting, or diarrhoea niay cause considerable transient 
elevation in the count of red cells, while sudden losses follow intes- 
tinal hemorrhage. Occasionally a very severe post-febrile anaemia 
occurs, the red cells being reduced nearly to 1,000,000 with the 
qualitative changes of a grave secondary anaemia. In most cases 
the qualitative changes are slight. 

2. Haemoglobin, as in most cases of anaemias, suffers somewhat 
more than the number of red cells. 

3. The number of leucocytes is subnormal throughout the dis- 
ease, averaging about 5,000 at its height, though much lower figures 
are common. This leucopenia progresses with the severity and 
duration of the infection. Cold baths cause an immediate transient 
increase in the number of leucocytes in the peripheral circulation, 
an increase which may amount to double or triple the number be- 
fore the bath. 

Differential counts show, during the febrile period, a progressive 
diminution in the number and percentage of the polynuclear cells, 
with a corresponding rise in the percentage of lymphocytes and 
large mononuclear cells, and a great diminution or even disappear- 
ance of the eosinophiles. In convalescence the percentage of eosino- 
philes markedly increases, often before the other forms have re- 
sumed their normal numbers. 

4. Most complications, especially inflammations, produce a leu- 
cocytosis, but a particularly malignant infection may be followed 
by no increase and even by a diminution in the number of leuco- 
cytes. In many of the leucocytoses following complications the 
percentage of polymorphonuclear cells does not rise. 

Diagnostic Value. 

There are few diseases (outside of those Known as diseases of 
the blood itself) in which the blood count is so often of value in 
diagnosis. The diagnosis of typhoid fever is made by exclusion — 
exclusion of other causes of fever and of local inflammatory proc- 
esses in particular. 



208 SPECIAL PATHOLOGY OF THE BLOOD. 

1 111 this process of exclusion the blood is a most powerful 
adjuvant, inasmuch as almost all local Inflaminntorij processes Jioiw 
leucocytosis, whUe typhoid (uncomplicated) does not. I recall two 
cases in which the chart and symptoms pointed to typhoid, but in 
which the persistent marked leucocytosis directed attention to the 
search for an inflammatory focus. Both were at first unattended 
with pain, tenderness, or other localizing symptom, l)ut later signs 
and symptoms began to point to the Ilvpr, from which pus was 
evacuated by puncture. These cases of ohsresses of the lirer are 
typical of the value of blood examination for any deep-seated su})- 
puration. I have seen good clinicians puzzled for twenty-four 
hours over the diagnosis between appendicitis and typhoid, but the 
indication of the blood count Avas always fulfilled. Pyaemic or 
septicsemic processes are usually distinguishable from typhoid by 
the same test — the presence of leucocytosis in the former. 

Of the value of the blood in distinguishing certain cases of i)neu- 
monia from t3'phoid I have already spoken on page 194, 

2. Aside from local or general pyogenic infections perhaps the 
disease most often confounded with tyjjhoid is malaria. This is 
especially the case in the southern part of this country, where for 
want of xjroper blood examination the confusion of the two diseases 
is indicated in such a term as " typhomalarial fever." Malaria and 
typhoid are alike in having no leucocytosis, but the presence of the 
malarial parasite is an absolute test and in marked cases is always 
decisive. Veiy mild cases of malaria may show so few organisms 
in the peripheral circulation that without prolonged search they 
cannot be found, and in the severest types of all the organisms are 
not very abundant. In the vast majority of cases, however, the 
organism can be readily found and our diagnosis made certain. 

3. Tuberculosis, local or miliary, if uncomplicated by any pyo- 
genic organisms, cannot be distinguished from t^'phoid by the blood 
count alone, as neither disease shows leucocytosis, but here the 
Widal reaction (see page 529) comes to our rescue. 

A large proportion of lymphocytes is commoner in typhoid than 
in tuberculosis, but it may occur in either disease. In the majority 
of cases, however, tuberculosis is complicated with septicaemia from 
a secondary pyogenic infection, and is then easily distinguished b^- 
the existence of leucocytosis. 

4. Typhus fever has not been well studied and the reports of 
its blood condition are contradictory. At present we cannot say 



TYPHOID FEVER. 209 

whether or not it can be distinguished from typhoid by the blood 
examination. In most cases the absence of a serum reaction will 
exclude typhus. 

5. Two cases of eiythema nodosum with fever between 101° and 
103° gave me trouble in diagnosis latel3\ In both the blood was 
normal and differed from typhoid only by the absence of a serum 
reaction. Thayer has reported a similar case {loc. cit., p. 530), in 
which, however, there was a marked leucocytosis throughout. 

6. Tricliiniasis may run a course quite indistinguishable clini- 
cally from that of typhoid, but the presence in trichiniasis of a 
leucocytosis with marked eosinophilia and the absence of Widal's 
reaction will decide any case of doubt. 

7. Most auto-intoxications (ptomaine poisoning) produce leucocy- 
tosis, and can therefore be distinguished from typhoid. 

8. Meningitis, especially in its epidemic cerebro-spinal form, 
has many symptoms like those of typhoid, but it always produces 
leucocytosis, and is never associated with Widal's serum reaction. 

9. From infJuenza typhoid cannot be distinguished by the blood 
count, as neither of them produces leucocytosis. Here the blood 
gives aid only through the serum reaction. 

10. Acute Infectious Dysentery/ may present (especially in the 
tropics) many features that remind us of typhoid. As a rule it 
produces no leucocytosis, but it is distinguishable from typhoid by 
the presence of Widal's reaction in the latter. 

The occurrence of complications in typhoid may mask its char- 
acteristic blood changes so as to make the blood useless in diagnosis; 
but in most early cases, in which the diagnosis is especially impor- 
tant and difficult, the blood shows no leucocytosis and is therefore 
of great value in the exclusion of other diseases. 

Prognosis. 

In prognosis Naegeli {loc. cit.) agrees with Turck in regarding 
the persistence or early reappearance of eosinophiles as a favorable 
sign, and believes that a normal number of poljmuclear cells is a 
good sign when the outlook is more serious, if the leucoC3'te count 
is very low and does not increase during complications. 
14 



210 SPECIAL PATHOLOGY OF THE BLOOD. 



DIPHTHERIA. 

Bacilli of diphtheria in ilu^ (nreulating blood are practically 
never to be found. 

The specific gravity, according to Grawitz, is ahnct' normal at the 
height of the disease. He obtained the same result experimentally 
by injecting cultures of the Klebs-Loffler bacillus into dogs and 
rabbits. He concludes that the poison of the disease is lympha- 
gogic and so concentrates the blood. 

Red Corpuscles. — Morse's' investigations show an average of 
5,100,000 in twenty cases counted during the first "week of the dis- 
ease and of 5,150,000 in 10 cases during the second and third week 
of the disease — practically normal figures. 

These are the first systematic'- investigations of the red cells in 
diphtheria and are confirmed by the reports of Ewing, Engel, and 
Billings. The latter observer in counts made in seven cases during 
the first five days of illness found an average of 5,600,000 -f- red 
cells per cubic millimetre. During the first five to ten days after 
this, the same cases showed an average loss of 510,000 cells per 
cubic millimetre; five out of the seven showing considerable losses, 
two remaining about the same. These were cases treated without 
antitoxin. The two cases showing no loss of red cells were both 
very mild, one having no membrane at any time. The diminution 
ranged from 470,000 (third day) to 2,040,000 (sixth day). As a 
rule no diminution can be made out until after the third or fourth 
day. 

Out of twenty-three cases treated with antitoxin and each 
counted several times over, only three showed any considerable 
diminution in the red cells and these lost less than 400,000 each, 
not much beyond the limit of error (200,000) allowed for by the 
investigator, and all of them severe cases. Six patients who were 
anaemic when admitted (average — 4,640,000) showed a steady rise 
in the red cells as the disease (treated with antitoxin) progressed. 

It is evident from these figures that antitoxin largely prevents 
the anaemia which usually develops in the first five to ten da3^s. In 
cases not treated with antitoxin the regeneration from the result- 
ing anaemia is slow. Healthy individuals injected with antitoxin 

' Boston Medical and Surgical Journal, March 7th, 189."5. 
•Earlier rejDoits are faulty as to technique. 



DIPHTHERIA. 211 

showed a very moderate reduction in the red cells in about one-half 
the cases, the greatest loss being 932,000 per cubic millimetre (fif- 
teen cases counted by Billings). 

Qualitative Changes. — Billings' careful study of stained speci- 
mens showed no deformities in size or shape and no nucleated red 
cells, but Engel has found normoblasts. Polychromatophilic red 
corpuscles were very few in tlie cases in which antitoxin was used, 
but more numerous when it was not used. 

Hannoglohin. — Here again the most thorough investigations are 
those of Billings. In cases treated without antitoxin there was an 
average loss of ten per cent, regained in part during convalescence, 
but as usual reaching normal later than the count of corpuscles. 
When antitoxin was given, the diminution of haemoglobin was less 
marked, but when the decrease did occur the return to normal was 
slow compared to that of the red cells, even when the patients were 
up and about and apparently well. 

White Corpuscles. — Leaving out the older observations in which 
the technique was probably faulty, the principal investigators are 
Morse, Ewing, Gabritschewsky, Billings, File, and Engel. 

All agree that a considerable leucocytosis is present in most 
cases — 34 out of 36 of Billings' cases, 26 out of 30 of Morse's (the 
latter made but one count in each case), 49 out of 53 of E wing's. 
In a general way, the severest cases show the greatest leucocytosis, 
but it does not follow the pulse, temperature, nor the extent of the 
membrane, and " the ordinary clinical examination of the patient is 
of much greater value in . . . prognosis . . . than any informa- 
tion to be gained from the examination of the blood. The latter 
is simply confirmatory, never indispensable" (Billings). Morse's 
conclusions are the same, although he considers that with notable 
exceptions the amount of membrane is a rough measure of the 
degree of leucocytosis. He finds no correspondence between the 
glandular swellings and the degree of leucocytosis, though he noted 
that "in the fatal ' septic ' cases with greatly enlarged glands,'^ very 
high counts were present. Other cases with little or no enlarge- 
ment of glands showed equally high counts, however. 

Ewing' s 4 cases without leucocytosis were all mild, but of Bil- 
lings' 2 cases without leucocytosis one was the severest of his whole 
series, while the other was mild. Of Morse's 4 cases without leuco- 
cytosis 3 were mild and 1 was severe. Gabritschewsky' s 14 eases 
all showed leucocytosis. 



212 SPECIAL PATHOLOGY OF THE BLOOD. 

Putting the results of these four observers together we see tliat 
when leucocytosis is absent the eases are either very mild or very 
severe, conditions analogous to those to be noted in pneumonia and 
septicaemia. The counts in recent epidemics range from normal to 
48,000 (Morse) or to 38,600 (Billings). Felsenthal ' found 148,229 
per cubic millimetre in one case, and Houchut's'^ counts are often 
over 75,000. 

In a general way the counts rise while the disease progresses and 
fall gradually as improvement goes on, disap})earing after tlie mem- 
brane. " The leucocytosis is well marked by the third daj' and very 
likel}^ earlier" (Morse). Billings found an increase after one day's 
illness, but usually less than was present later in the disease; one 
of his cases, however, had a higher count on the first day of the 
disease than on any subsequent day, though no antitoxin was 
given. 

The injection of antitoxin has apparently no effect upon the 
leucocyte (strange to say) except in the first twenty-four hours after 
its use. Immediately — I.e., within thirty minutes after an injec- 
tion — the leucocytes are stated by Ewing to be considerably dimin- 
ished, V)ut the leucocyte curve does not reach normal any sooner 
than in cases in which no antitoxin is given, although it begins to 
fall in the majority of cases after the injection. The same thing 
(according to Billings) takes place without antitoxin. 

The leucocytes of healthy persons are likewise unaffected by 
antitoxin injections. 

Qualitative Changes. — All authors agree that in most cases the 
neutrophiles are increased. Morse found an average of 80 per cent 
in 26 of his 30 cases. Of the other 4, 1 was normal and 3 were 
subnormal (58, 59, and 59 percent); 2 of these were convalescent, 
the other had been sick a week and had 12,000 white cells per cubic 
millimetre. A marked lymphocytosis was present in 2 of Swing's 
53 cases, 43,200, and 13,950 absolute.' In Billings' cases the 
polymorphonuclear varieties averaged 80 per cent and the lympho- 
cytes 19 per cent, the eosinophiles being reduced to 1 per cent on 
the average and often being entirely absent. With- Morse eosino- 
philes averaged 2 per cent. 

^ Arcliiv f. Kinderheilk., vdI. xv., p. 78. 1893. 
-Comptes Rendus, 1877, Ixxv., No. 3. 

■^In a case of Rieder's, aged three years, the lymphocytes rose from 19 
per cent during the fever to 64 per cent \u convalescence. 



i 



DIPHTHERIA. 218 

The proportion of polymorphonuclear cells is usually directly 
proportional to the total increase of leucocytes. 

Ewing thinks that "the staining reaction of the leucocytes is an 
accurate measure of the severity of the diphtheritic infection," and 
this staining reaction he finds increased in favorable cases b}' the 
injection of antitoxin. 

Billings did not find any such changes in "staining reaction," 
though he claims to have carefully followed out Ewing's procedures. 

Pitkianen ( 6^«^. din. de Botlcin, 1901, p. 1033) states that in 
unfavorable cases the eosinophiles disappear by the third or fourth 
da}', and the percentage of polynuclears is persistently elevated. 
If the eosinophiles are constantly to be found, the prognosis is 
good. In convalescence they rise above normal. He contrasts the 
presence and steady increase of these cells in scarlatina with their 
diminution in diphtheria (until convalescence) and considers the 
difference to be of diagnostic value. 

Engel ^ found that antitoxin at first slightly increased the i)er- 
centage of lymphocytes, and sometimes this increase was very 
marked. In one case the lymphocytes increased from 24 to 65 per 
cent after antitoxin. 

The point on which he specially insists is the jjresence of con- 
siderable numbers of myelocytes in fatal cases. 

Of the patients examined by him 17 died, and 9 of these had 
from 36 to 168 myelocytes in every one thousand leucocytes. 
Myelocytes were also present in some of the patients who recovered,, 
but in smaller numbers (1.3 to 1.5 per cent). 

In one case he found on the third day of the disease 4.3 per 
cent of myelocytes, and from this point the percentage gradually 
rose to 13.8 per cent, and then fell, there being 1.7 per cent pres- 
ent at the time of death. An abscess occurring in the case showed 
only the usual polymorphonuclear leucocytes in its contents. He 
concluded that a large percentage of myelocytes is a bad prognostic 
sign in any case. 

Myelocytes are not mentioned in any of the numerous differen- 
tial counts made by Gabritschewsky, Ewing, Morse, and Billings, 
so that Engel' s observation is so far unique. 

lodophilia is usually present. 

1 Gesellsch. f. iunere Med., Berlin, July 6th, 1896. 



214 SPECIAL PATHOLOGY OF THE BLOOD. 

Suianiary. 

1. Moderate anaemia, especially in cases treated without anti- 
toxin. Eegeneration is slow. 

2. Leucocytosis, very roughly parallel to the severity of the 
disease, unaffected by antitoxin treatment, gradually decreasing as 
the disease passes off, sometimes absent in very mild or very severe 
cases. 

3. Polymorphonuclear leucocytes much increased during febrile 
stages, often diminished in convalescence. 

4. Myelocytes numerous in some severe cases. 

The blood examination has no diagnostic value so far as I can 
see; in prognosis the absence of leucocytosis (except in obviously 
mild cases) and the presence of many myelocytes are apparently 
bad signs. 



1 



CHAPTER IV. 

ACUTE INFECTIOUS DISEASES (CONTINUED). 
SCARLET FEVER. 

Heubner' noted hsemoglobinsemia in one -case. Fibrin is not 
increased even at the height of the fever, provided inflammatory 
complications are absent. 

Red Cells. — Very little is to be found in literature upon the sub- 
ject. Kotschetkoff ^ noted a gradual diminution of the red cells to 
about 3,000,000, regeneration taking place in the course of not less 
than six weeks. Other observers have found little or no anaemia. 

Hayem ^ estimates the average loss of red cells at 1,000,000. In 
mild cases he finds the lowest figures on the first day of normal 
temperature. In severer cases in which the fever comes down 
slowly, the red cells may not reach their minimum till twenty-four 
hours after the normal temperature is regained. 

Felsenthal * in six cases found the count to be 4,500,000 to 
5,500,000 — no considerable variation from normal. 

Zappert " in six cases found it to be from 3,920,000 to 4,500,000, 
an average of 4,150,000. Normoblasts are occasionally seen — as 
in one of Tiirck's cases, and the normal variations in size and shape 
are exaggerated. 

Wliite Cells, — Most observers are agreed that leucocytosis is the 
rule, contrasting in this respect with measles, in which no leucocy- 
tosis occurs. The increase attains its maximum two or three days 
after the eruption. In light cases it may sink to normal even be- 
fore the fever is gone, while in severer cases it may persist several 
days after normal temperature is reached. Yon Limbeck had a case 
in which the leucocytosis persisted for twelve days after the teni- 

'Deut. Arch, f. klin. Med., vol. xxiii, 

2 Ref. in Petersburg, med. Woch., 1892, 1. 

^ Loc. cit., p. 914. 

^Arch. f. Kinderheilk., 1892, p. 80. 

^Zeit. f. klin. Med., 1893, p. 292. 



216 SPECIAL PATHOLOGY OF THE BLOOD. 

perature had become noiinal. Forty tliousand per cubic millimetre 
is not unusual in well-marked cases. Eieder's ten cases averaged 
17,500; Felsenthal's six counts were between 18,000 and 30,000. 
My own are similar. 

In a general way the severest cases are apt to have the highest 
leucocyte counts; the figures have no direct relation to the amount 
of fever, glandular swelling, or to complications in the ear or 
kidney. 

Van den Berg {Archiv fiir Kinderheilk., 1898, vol. xxv., p. 321) 
in 12 cases found the red cells in uncomplicated cases usually 
above 4,000,000. Endocarditis or nephritis, he found, reduces the 
erythrocytes and haemoglobin very rapidly, and in some cases as 
low as 2,000,000 with 25 per cent haemoglobin. 

The leucocytes averaged about 17,000, but 2 cases exceeded 
30,000; the increase lasted from twenty to thirty days. 

Mackie (Lancet, 1901, vol. ii., p. 525) found leucocytosis in 
each of 25 cases, one case reaching 93,300; but in no case was the 
leucocytosis present until the day after the appearance of the rash. 

Rechzeh (Zelt. f. klin. Med., 1902, p. 107) studied ten cases 
and noticed as a rule no changes in the number of red cells nor in 
the haemoglobin. Poikilocytosis and erythroblasts were occasion- 
ally noticed. The leucocytosis he found to run parallel with the 
fever curve, reaching the highest figures when the rash was at its 
worst, and then rapidly falling. 

Eegarding the percentages of the different leucocytes he con- 
firms the findings of earlier writers. 

Sacquepee {Arch. f. Med. Exp., 1902, p. 101) made 50 counts in 
14 cases and reached the following conclusions : 

1. About the third day of the illness there is a marked and 
sudden rise in the absolute and relative number of polynuclear with 
a slight absolute increase of lymphocytes. This raises the total 
leucocyte count often to 20,000, once to 31,000; 85 to 90 per cent 
of this increase is made up by the polynuclears. This increase 
rarely lasts beyond the seventh day, and by the twentieth day the 
total count is generally subnormal. There is no parallelism be- 
tween the count and the severity of the disease. 

2. Beginning about the fourth day, there is an eosinophilia 
(highest, 13 per cent or 1,950 per cubic millimetre) which falls ver}^ 
slowly so that even in the third or fourth week the eosinophiles are 
above normal. 



SCARLET FEVER. 217 

3. In the second week there is a slight absolute increase of 
lymphocytes. 

4. Streptococcus complications raise the number of polynuclear 
cells and depress the eosinophile count. 

Qualitative Changes. — The polymorphonuclear forms are in- 
creased, often to ninety per cent, soon falling except in the worst 
cases. The peculiar characteristic of the disease is the persistence 
of eosinophiles in all but the severest cases despite the increase of 
polymorphonuclear forms. The only other infections of which this 
is true are tetanus and acute articular rheumatism. They may run 
as high as five per cent during the fever, and are still more numer- 
ous in convalescence, remaining increased for six weeks. According 
to Kotschetkoff, disappearance of eosinophiles is a bad prognostic 
sign except at the very beginning of the fever, when they may be 
temporarily absent in favorable cases. Presumably they have some 
connection with the exanthem, eosinophilia being so common in 
connection with skin lesions. They may number 15 to 20 per cent 
of the leucocytes in convalescence (Bensaude). Tiirck reports 14.3 
per cent (1,800 absolute) in one case and 13.3 (800 absolute) in 
another. Felsenthal's average is 5 per cent; Zappert's, 3 per cent. 
The lymphocytes are decreased proportionately to the severity of 
the case, the worst cases showing only 2 to 4 per cent. 

An increase of eosinophiles during a scarlatinal nephritis is re- 
garded by Keusser and his pupils as a favorable sign, and their 
absence as ominous. In ordinary cases without nephritis they reach 
their maximum in the second or third week and are not normal till 
the sixth. In the active stages of the disease myelocytes, transi- 
tional neutrophiles, and "stimulation forms'' occur. 

Summary. 

Slight anaemia. 

Leucocytosis beginning just after the eruption and often lasting 
about a week. 

Eosinophiles increased from the fourth day until late in conva- 
lescence. 

Diagnostic and Prognostic Value. 

1. The chief importance of the blood examination is in distin- 
guishing the disease from measles and the eruptions of other dis- 
eases. Measles has no leucocytosis. 



218 SPECIAL PATHOLOGY OF THE BLOOD. 

2. Whether the prognostic significance- attached by Neusser and 
others to the percentage of eosinophils is genuine or not, cannot 
as yet be positively stated. 

MEASLES. 

In mild cases the blood shows no changes at all. When bron- 
chitis, coryza, and conjunctivitis are very marked, fibrin ma}' be 
increased. 

Red Cells. — In mild cases no change — never over 400,000 or 
500,000 red cells are lost (Hayem). Felsenthar.s eight cases 
showed counts of 5,000,000 to 5,500,000. 

White Cells. — There is no leucoeytosis, often a leucopenia dur- 
ing the eruptive stage. In convalescence the lymphocytes and 
especially the large mononuclear forms are increased. Felsenthal 
in eight cases found the count normal or diminished. Pee found 
but 4,000 in a ease with a fever of 102.7''. Eieder's eight cases 
averaged 7,500, being lowest at the height of the disease and increas- 
ing as fever passed off. Complication with catarrhal pneumonia or 
a very bad bronchitis and coryza, may slightly raise the count. 
The eosinophiles, contrary to the example of scarlet fever, are often 
diminished during fever. 

Combe (Arch, de Med. d. Enf., 1895, vol. ii., p. 345) found in 
the incubation (never later) a polynuclear leucoeytosis. As the 
rash appears this leucoeytosis disappears and leucopenia takes its 
place. 

Plantenga {ibidem, March, 1903) confirms these findings in 
twenty-nine cases. A '' distinct and constant leucoeytosis '" occur- 
ring in mcubation and rising as high as 20,000 with 75 per cent of 
polynuclear cells gives way to leucopenia when the rash comes out. 
The eosinophiles are diminished or absent during the fever. 

Renaud (^TJiese de Lausanne, March, 1900) also confirms Combe's 
findings and thinks the pre-eruptive leucoeytosis of diagnostic value. 
This increase and the subsequent decrease concern wholly the poly- 
nuclear cells. He generalizes from six cases. 

Courmont studied also six cases (Gaz. des Hop., 1901, p. 1001) 
and agrees in the main with Eenaud but finds some polynucleosis in 
the eruptive stage. Myelocytes (he agrees with Weil) are absent. 
In measles occurring in adults Courmont finds a slight polynuclear 
leucoeytosis at the outset, and in this he agrees with Weil {These 
de Paris, ^^ 1900, four cases). 



MEASLES. 



219 



Rechzeh {loc. cit.) in ten cases got practically similar results, 
and was struck with the fact that the blood presents a picture 
almost the opposite of that in scarlatina. 

Tilestoii {Boston Med. and Surg. Jour., 1904) in twenty-five 
cases found no leucocytosis in the prodromal or eruptive stages, 
though the percentage of polynuclear cells was usually increased. 
Later this increase was replaced by a slight increase in the lympho- 
cytes. Eosinophiles and blood plates were diminished until conva- 
lescence, when the former became normal or slightly increased. 
All complications produced leucocytosis, and in every case the occur- 
rence of leucocytosis could be explained by a complication. 

The Massachusetts General Hospital records furnish the follow- 
ingc counts in eleven cases : 









Table XIII.— 


Mf.asles, 










Per cent 




Xg^. 


Sex. 


Red cells. 


White cells. 


haemo- 
globin. 


Remarks. 


4 






11,000 




Rash out; temp. 104\ 


11 






10.100 






38 


^[. 


4,700,000 


9,000 


65 


" Black measles " ; petechiae. 


8 


M. 




9,000 




Differential count normal. 


21 






8,200 




Rash out; temp. 108\ 


23 


F. 




8.000 


68 


104° ; eruption out. 


4 


M. 


5,000,666 


7,000 


60 


Eruption just out. 


10 


M. 




6,000 

6,000 
6,000 


•• 


103°; three days before the erup- 
tion ; differential count nomial. 
Eruption out one day. 
Eruption out three days. 


53 


F. 




3,500 






33 


F. 




8,500 


67 




14 






1,400 







The value of the blood examination is considerable in exclud- 
ing scarlet fever, diphtheria, and syphilitic roseola, all of which 
show leucocytosis. It cannot apparently be distinguished by the 
blood count from rotheln (German measles). 



ROTHELN (GERMAK MEASLES). 

Plantenga (loc. cit.) in nine cases found the blood like that of 
measles. I have seen two cases with 6,000 and 8,000 leucocytes, 
respectively. 



220 SPECIAL PATHOLOGY OF THE BLOOD. 



MUMPS. 

Seven cases of mumxjs under my care showed no leucocytosis. 
One case with orchitis showed 19,400 leucocytes and 90 per cent 
haemoglobin on July 1st; 14,600 leucocytes on July 3d, and 17,000 
July 5th. 

Sacquepee (Joe. elf. ) records 30 counts in 15 cases. At the be- 
ginning of the disease he finds in about one-half the cases a slight 
increase in the total count (highest 13,600) 10 cases had never more 
than 12,000. The increase is largely in the lymphocytes. The 
polynuclears averaged 54 per cent, and in 2 cases were 16 per cent 
and 25 per cent, respectively. The eosinophiles averaged 0.7 per 
cent (subnormal). In 5 cases with orchitis he found a polynuclear 
leucocytosis (10,000 to 18,000). 



WHOOPING-COUGH. 

Meunier (^Archives d. Maladies de VEnfance, April, 1898) re- 
ported studies in 102 cases of whooping-cor gh= Lymphocytosis is 
early and constant. The counts average 22,700 in the cases exam- 
ined during the catarrhal stage and before the advent of typical 
" whooping " paroxysms. In the paroxysmal stage the leucocytes 
average 40,000 — the maximum being 51,250. In infants under four 
years the leucocytosis is far more intense than in older children. 
After the fourth year the count runs from 12,000 to 18,000. All 
the varieties of leucocytes are increased, but the lymphocytes are 
relatively as well as absolutely increased — a true lymphocytosis 
perhaps due to stimulation of the bronchial lymph glands. The 
increase begins in the earliest stages of the disease before the cough 
begins and persists into convalescence. 

Meunier found no such changes in the blood of cases of bronchitis 
or tracheitis, and suggests that the blood count may be of use in the 
investigation of doubtful epidemics in schools or hospitals. Cima 
(Fedriatria, 1899, :N"o. 9), Stengel and White {Univ. Penn. Med. 
Jhdl.j November, 1901, and De Amicis and Pacchioni {Clin. 
Medlca, 1899, vol. iv., p. 103) confirm these observations, though 
in their cases the average lymphocytosis was somewhat less — 
17,900. 



SMALLPOX. 



221 



The following cases exemplify these rules (see also page 193). 
Table XIV. — Whooping-Cough. 



Age. 



Red cells. 



White cells. 



Per cent 
haemoglobin. 



5,193,000 



75,000 



26.500 



32,800 



47 



July 23d. 
Polynuclear, 
Lymphocytes 
Eosinophiles, 
August 19th. 
August 31st. 
Polynuclear, 
Lymphocytes, 43. 
Eosinophiles, 1. 
Lymphocj^tes, 69, 



43. 

57. 

1. 



56. 



Steven {Lancet, vol. xx., 1902) reports a case of "broncho- 
pneumonia" with paroxysms of convulsive cough and cyanosis. 
Tlie blood count is remarkable, but points, I think, to pertussis as 
the most probable diagnosis. I have seen two similar cases (see 
pages 193 and 106). Stevens' figures areas follows: Red cells, . 
4,800,000; hgemoglobin, 100 per cent; leucocytes, 236,000. Of 
these there were: Polynuclears, 33.6 per cent; small lymphocytes 
50.2 per cent; large mononuclear, 15.2 per cent; eosinophiles, 1 
per cent. 

YACCINATION ANDYACCINA. 

Billings * and Sobotka ^ found leucocytosis reaching its height 
(15,000) with the maturity of the vaccine pustule, and composed 
chiefly of polynuclear cells; but in adults' blood Courmont and 
Montagnard ^ found nothing abnormal after vaccination. 

In generalized vaccinia Enriquez and Sicard * found the blood 
normal. 

SMALLPOX (VARIOLA). 

Red Cells. — According to Hayem no other fever is so destruc- 
tive of red cells. During the fever the count is normal or increased, 
but when the temperature falls permanently the number of red cells 
falls suddenly, whether because the blood is diluted (see above, page 
188) or by a real destruction. From this time on the cells are 
slowly regenerated; even at the fifteenth day Hayem found them 
considerably below normal. 

'Billings: Med. News, 1898, p. 301. 

2 Sobotka: Zeit. f. Heilk., 1893, p. 349. 

^Courmont and Montagnard: Jour, de Phys. et Path. Gen., 1901, p. 63. 

^ Enriquez -Siccard: Soc. deBiol., December 1st, 1900. 



222 SPECIAL PATHOLOGY OF THE BLOOD. 

In liemoiThagic cases the anaemia comes on more quickly, its 
degree depending on the amount of hemorrhage. In one patient, ■ 

dying on the seventh day of the eruption, Hayem found but 2,000,- 
000 red cells, in another at the same stage, 4,f)00,000. 

Fibrin is not increased until the stage of suppuration is leached. 

LpMcocytes. 

In Pick's report on 42 cases no leucocytosis is recorded until the 
appearance of vesicles. 

Elaborate studies in the blood of smallpox have lately l)een pub- 
lished by Weilji and by Courmont and Monta guard.- These studies 
are concerned especially with the leucocytes. In Weil's series of 
36 cases the counts ranged between (3,000 and 10,000 in 6 cases, 
between 6,000 and 13,000 in 13 cases, exceeding 15,000 in 9 cases, 
exceeding 20,000 in 3 cases, 25,000 in 3 cases, .*^)0.000 in 1 case, 
35,000 in 1 case. 

One case ranged from 3,000 to 6,000 during the whole course of 
the disease, except on the day of vesiculation (21,000), but this is 
very rare, and the leucocytes are usually increased from the begin- 
ning. The increase is usually most intense at the time of vesicula- 
tion, and from that time does not vary notably until after j^ustulation 
Avhen it slowly declines until in convalescence a subnormal count is 
reached. In hemorrhagic cases the increase is usually less marked. 

A sudden drop in the leucocytes count may occur in the fatal 
suppurating or hemorrhagic form. For example, in two fatal sup- 
purating cases the leucocytes dropped from 24,000 and 18,000 to 
6,200. In one hemorrhagic case on the dying day counts of 6,200, 
6,000, and 4,400 were recorded. A sudden drop in the leucocytes 
is then a bad prognostic sign (from this opinion Courmont and 
Montagnard dissent). 

Complications occurring in convalescence protluce a second rise 
in the leucocytes. 

Qualitative Changes. 

The most significant fact in the blood of variola, according to 
the writers already quoted, is the increase in mononuclear cells. 
The percentage of polynuclear cells, instead of being increased as in 
most infectious diseases, is from the outset diminished (i.e., 40 to 
50 per cent), and may go as low as 14 to 20 per cent. Eosinophiles 



1 Soc. de Biol., June 29th, 1900. 

2 Soc. de Biol., June 22d, 1900; Julv 6tli, 1900. 



SMALLPOX. 223 

range from normal (1-3 per cent) at the beginning of the disease, 
downward. They are lowest just before desquamation. In conva- 
lescence they are often slightly increased. 

Among the " mononuclear cells '* the increase of whicii is held 
by Weil to be characteristic of the disease are : 

(o) Small lymphocytes, 30-40 per cent. 

(6) Large mononuclear, 4—10 per cent. 

(e) Myelocytes, 2-10 per cent (even 25 per cent in hemorrhagic 
cases). 

(d) Ttiick's ••Reizungsformen," 2-10 per cent. 

During suppuration and desiccation the mast cells are sometimes 
increased (5 per cent). The almormal leucocytes — (c) and (c?) 
above — are present from the very beginning of the disease and form 
a very characteristic part of the blood picture. They persist through 
pustulation and dim.inish only in convalescence. They are present 
in mild varioloids as well as in severe variola. Complication (pneu- 
mococcus or streptococcus septicaemia) do not materially modify the 
blood picture, unless they occur late in convalescence. In conva- 
lescence a polynuclear leucocytosis may result from suppurative 
complications. 

Di'tgn ostic Value. 

In excluding scarlatina, measles, purpura, sj^philis, erythema 
multiforme, the blood is conclusive. Varicella, on the other hand, 
produces changes in the blood which are precisely of the same 
type as those of variola, though less in degree. 

VARICELLA (CHICKEX-POX). 

The first observation of wliich I am aware is that reported by 
Engel.i In a child of five he found during the height of the pus- 
tular stage a moderate leucocytosis, with 67 per cent of neutrophiles 
(high for a young child), and no eosinophiles. Three days later, 
as the pustules were healing, the neutrophiles had sunk to 47 per 
cent (normal for that age) and the eosinophiles had risen to 16 per 
cent. 

Xobecourt and Merklen (Journ. de PJiys. et Path. Gen., May, 
1901) studied 15 cases and found in 10 of them a normal or subnor- 
mal leucocyte count and in 5 a very slight increase (highest = 

14,500). 

^ 15tli Couir. fur iuuere 3Ied., 1897. 



224 SPECIAL PATHOLOGY OF THE BLOOD. 

The polyiLUclear cells were increased in 6 and diminished in 7. 
The eosinophiles were always scanty; 5 of tlie patients showed 
myelocytes, one as high as 12.5 per cent. On the whole the blood 
seems not to be distinguishable from that of variola, although in 
most eases the total leucocyte count and the percentage of myelo- 
cytes are higher in variola. 

Stengel and White (Joe fit.) found nu leucocytosis in 2 cases, 
12,800 in a third, and 19,200 in a fourth, which later developed 
})neumonia. 

ACUTE ARTICULAR RHEUMATISM. 

According to Hayem and Garrod ' the blood constitutes, as in 
syphilis, a most valuable measure of the intensity of the sickness, 
which is parallel to the severity of the blood-changes rather than to 
the number of joints affected. TJie fever, the intensity of the 
lesions, and the state of the blood run parallel, in a general way, 
but the degree of anaemia is a more delicate index of the patient's 
condition than even the temperature chart (Garrod). 

Tlie Blood ns a Whole. 

Fibrin is greath' increased. In no other disease except in pneu- 
monia is the network tliicker or more rapid in formation. Accord- 
ing to Maclagan, this is to he explained by an increase of tissue 
metamorphosis. Coagulation, on the other hand, is not quicker, 
but slower than usual. 

Lactic acid is present in excess, but cannot be clinically esti- 
mated, nor is its excess peculiar to this disease. 

The alkalinity of the blood had been reported diminished, but 
the technique is not considered reliable by the best observers. 

Bed Cells. — -Hayem- and Osier' state that the poison of acute 
rheumatism is a powerful and rapid destroyer of red cells. In 
acute cases, according to Hayem, the red cells lose at least 1,000,000 
of their number, and in cases which drag along and relapse the loss 
is from 1,500,000 to 2,000,000. When an attack is cut short by 
salicylate treatment the drain on the corpuscles is stopped. Ttirck's 
careful studies led him to the same conclusions. Eed cells and 
haemoglobin are always markedly diminished during the fever, the 
hsemoglobin especially, and after the attack a post-febrile anaemia 
of varying severity is always left. 

' British Medical Journal, May 28th, 1892. 
'■^ Loc. cit., p. 9] 7. 3 " Practice of Medicine.'' 1895. 



ACUTE ARTICULAR RHEUMATISM. 225 

So far as my experience goes, this diminution does not seem to 
occur in all cases. Many of my cases had been sick some weeks 
before the time when the count was made, jet the counts are not 
very low. The average count of red cells in the whole group of 
cases is 4,300,000. The lowest counts were 2,528,000 with 45 per 
cent of haemoglobin, 3,248,000 with 45 per cent of haemoglobin, 
3,456,000 with 50 per cent of hemoglobin, 3,332,000 with 45 per 
cent of haemoglobin, 3,468,000 with 36 per cent of haemoglobin, 
3,440,000 with 26 per cent of haemoglobin, 3,608,000 Avith 40 per 
cent of haemoglobin. Only 13 cases below 4,000,000 are recorded 
out of 113. McCrae ' in 69 cases found the average to be 4,532,000 
at the beginning of the disease and observed no diminution during 
the later course of most of the cases. 

Qualitative Changes. — Maragliano'S so-called degenerative 
changes in the red cells have been observed in this disease, but 
are not very marked. Tlirck found erythroblasts in about a 
quarter of his cases. Deformities in the red cells are usually 
slight. 

Hoimoglohin. — As in all secondar}^ anaemias the coloring matter 
is diminished more than the count. The average haemoglobin per- 
centage in this series is sixtj'-three, and the color index .73. 
McCrae (loc. clt.) states the average of haemoglobin in 77 cases as 
66 j)er cent, a figure practically identical with mine. The most 
marked change occurring in any case was a loss of 20 per cent in 12 
days, the count of red cells being unchanged. 

Leucocytes. — All observers agree that leucocytosis is the rule and 
that its degree is roughly parallel to the acuteness and severity of 
the attack (the individual's vigor of reaction is always a factor) and 
the amount of fever. Ttlrck insists that complications (pneumonia, 
pericarditis, pleurisy) are present whenever the count rises over 
20,000, and in this he is supported by Ewing. No such complica- 
tions were discovered in many of the cases of Table XY. which exceed 
20,000, but this table shows that in 80.5 per cent of 243 cases the 
leucocytosis was under 18,000. McCrae 's average in 83 cases is 
11,700; mine in 243 cases is 13,800. In 29 of his cases the count 
was 10,000 or less. Tlie remaining 54 cases average 14,260, or 
15,380 if the highest count is taken in each case. There were 17 
cases with over 15,000 leucocytes, 4 with over 20,000, and 1 of 
38,000. All cases complicated with pericarditis showed leucocj'- 

'^IcCrae: f. Am. Med. Ass., January 24th, 1903. 
15 



226 



SPECIAL PATHOLOGY OF THE BLOOD. 



tosis, but no constant connection between leiicix-ytosis and en- 
docarditis. 

Rogers' noted leucocytosis (13,500 to 55,000j in 21 out of 23 
cases. The following tables illustrate the variations of the leuco- 
cytes in a fairly typical way : 

Table XV., A. — Acute Articular Rheumatism. 



i 


Age. 


i 


1 


21 


M. 


2 


20 




8 


.'>9 


F. 


4 


20 




5 


.33 


M. 


6 


Adult. 


M. 


7 


19 




^ 


7 




9 


23 




10 


23 


M. 


11 


49 


M. 


12 


46 




13 


21 


F. 


14 


37 




15 


24 


M. 


1« 


32 




17 


13 


F. 


18 


12 


M. 


19 


8 




2() 


20 




21 


23 




22 


19 


M. 


Z^ 


41 




24 


9 


F. 


25 


47 


M. 


2« 


25 


F. 


27 


18 


F. 


28 


19 


M. 


29 


19 


M. 


m 


29 




•M 


30 




82 


32 




33 


29 


M. 


34 






35 


37 


F. 


36 


30 


F. 


37 


47 


M. 


m 


27 


F. 


39 


17 


M. 


40 


27 


M. 


41 


28 




42 


33 


M. 


43 


42 




44 


33 




45 


26 




4fi 


10 




47 


20 


F, 


48 


36 




49 


28 


M. 


5(1 


Adult. 


M. 


51 


29 


M. 


52 


30 


F. 


53 


28 




54 


14 




55 


23 


•• 



Duration. 



5 weeks. 
........ 

? 
2 weeks. 

V 

? 

? 

? 
4 weeks. 

? 

2 days. 

1 day. 

2 weeks. 



Iday. 
3 days. 
2 months 



1 month. 



4 weeks. 

3 days. 
1 week. 

10 days. 

4 weeks. 



weeks. 



Degree of 
Inflamuiatiun. 



Red and hot. . . . 
? 

Tender and hot. 



Red and hot. 

V " " 



Red and hot . 
Red and hoi . 



Red and hot 



Red and hot 

Tender and hot. . 
No redness or 
beat. 



Swollen and ten- 
der. 



Very slight . . . 
Hot and red . . 



Some joints hot., 



Red 

cells. 



4,160,(XX) 
3,8:32,rHJO 
5,476.0(X) 
4,392,0(M) 
4,8;>2,(KX» 
4,21t).(»(M) 
3,24H.<)0; 
4,184.(XK 
3,792.(HK) 
5,192,()0(J 
4,8(KMKK) 
4,9;U.(K)0 
3.944,OfX) 
5. 224, (K to 
4,6(Xi.(l0n 
4,K5;i.(HK) 
4,m).n(K) 
4,4(Xt,(XX:) 
3,972.fXX) 
4,872.0(X) 
5,336.(XX) 
4,760,()0( 
4,397,000 
4,240.0(X) 
4,750.0(X 
4,8r)0,fK)(J 
4,156,000 

4,172,0fK^ 
4,580.(100 
4,720,a;0 
3,4o6.(XX) 
5,440,(XX) 
4,320,000 
4,128,000 
5,320,000 

4,160,000 
4,288,000 
3,580,000 
4,600,000 
4,200.000 
4,888.000 
5,480,000 
3,882,000 
4,056,000 
4,728,000 
4,312,000 
3,468,000 
4,716.(:KK3 
3,608,000 
3,768,000 
4,104,000 
3,440,000 
4,412,000 
4,240,000 
2,528,000 



White 
cells. 



31,5(X) 
27,8iK) 
27,(XX) 
26,(KX) 
24,5(KI 
2].(XtO 
20,(KH) 
1<).S(K) 
\S),(M) 
18,;}(K) 
17,7(X) 
17,400 
17,000 
lfi,;W(l 
1(),(KX) 
15.S(H) 
]5,2(W 
]5.(XXJ 
15,000 
15,0(XJ 
15, OCX) 
14.5(X) 
14,5(K) 
14.:386 

\um 

14.(KX) 
14,(X)0 

14,000 
13,500 
13.200 
13,000 
12,800 
12,750 
12.650 
12,5a) 

12,000 
12.000 
11,600 
11,500 
11,500 
11,300 
11,000 
10,400 
10,200 
9,400 
9,100 
9,000 
8,000 
7,000 
6.800 
5,500 
4,700 



Remarks. 



Knees and one ankle. 
Patient pale. 



Died. 

Third day. 
Temperature, 100*. 
Paronychia also. 



Cheeks rosy. 



Temperature 102*. 



Severe case. 
Seventieth daj. 



Hands alone Involved. 



Mitral regurgitation. 



Fourth relapse. 
Specific gravity, 1.040. 



Twenty-second day. 



Rogers: Lancet, September 6th, 1902. 



ACUTE ARTICULAR RHEUMATISM. 



227 



Table XV., B. — Acute Akticulak Rheumatism with Comp ligations. 



No. 


Age. 


Reds 
cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


32 





31,000 
25,000 
24,000 
12,(J0O 


40 


January 15th. Pericarditis, 
January 21st. 
January 26th. 
P'ebruary 2nd. 


2 


8^ 




28,900 
20,800 
17,500 
20,800 
14,700 
7,700 


65 


November 24th. Endocarditis. 

November 28th. 

November 30th. 

December 3rd. 

December 8th. 

December 11th, 


3 


18 





27,000 


90 


Mitral and aortic insufficiency. 


4 


44 


4,668,000 


23,100 
37,000 
47,330 


50 


April 12tb. Mitral insufficiency. 

April 14th. 

April 21st. Death. 


5 


13 





22,400 


75 


Mitral insufflciencv. 


6 


23 




21,600 
11,400 


80 


February 25th. Mitral insufficiency. 
March 8th. 


7 


34 





21,000 


85 


Mitral insufficiency. 


8 


43 




20,600 
14,200 


75 


April 30th. Mitral insufficiency. 
May 4th. 








8,200 


80 


May 14th. 


9 


25 




20,350 
16,600 
15,400 


60 


June 1st. Pericarditis with effusion. 
June 3rd. Acute endocarditis. 
June 5th. 


10 


18 




19,700 


85 


Mitral regurgitation. 


11 


3;^ 




19,400 


70 


Mitral stenosis. 


12 


24 




19,300 

15,300 
13,200 
14,300 
21,000 
30,300 
33,100 
16,400 
14,100 
18,000 
18,600 
20,900 
18,000 
18,000 
12,0('0 


80 
70 


December 7th. Pericarditis ; endocarditis ; mitral 

insufficiency and stenosis. 
December loth. 
December 12th. 
December lath. 
December 21st. 
December 23rd. 
December 24th. 
December 26th. 
December 29th. 
January 1st. 
January 5th. 
January 7th. 
January 9th. 
January 13th. 
January loth. 
February ^nd. 


i;i 


23 




18,800 


74 


Mitral insufficiency ; aortic insufficiency. Flint. 


u 


25 




18,400 
13,880 
11,500 


70 


Julv 24th. Mitral insufficiency. 
July 26th. 
July 30th. 


15 


24 


^ 


18,00(J 


8.5 


Mitral insufflciencv. 


Ifi 


24 




17,000 


90 


Mitral insufficiency. 


17 


22 




16,500 


80 


Acute nephritis. 


18 


a5 




14,700 
24,300 
13,400 
13,100 
0,450 
19,600 


70 


June 12th. Pneumonia. 

June 17th. 

June 21th. 

June 24th. 

June 26th. 

June 29th. 


19 


58 




14,260 


58 


Mitral insufficiency and stenosis; acute insuffi- 
ciency. 


20 


26 




14,200 


90 


Purpura. 


21 


40 




13,500 


85 


Chronic rheumatism ; cerebral hemorrhage. 


Zi 


18 




13,300 


85 


Mitral insufficiency. 


^8 


46 




11,500 


70 


Chronic nephritis. 


2i 


18 




11,000 


90 


Mitral insufficiency. 


25 


30 




10,000 


90 


Mitral insufficiency. 


26 


24 




10,000 


85 


Aoriic Insufficiency. 


27 


30 




9,800 


75 


Chronic interstitial nephritis. 


28 


16 




8,400 


85 


Mitral disease. 


29 


26 




8,400 


75 


Mitral insufficiency and stenosis. 


m 


23 


3,892,000 


8,400 


23 


Chlorosis. 


81 


34 


3,238,000 


8,000 


40 


Mitral insufflciencv. 


32 


46 




7,000 


80 


Mitral insufflciency. 



228 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XV., C. — Acute Akticulak Rheumatism. 

White Cells. Cases, 

Between 6,000 and 8,000 11 

8,000 " 10,000 30 

10,000 " 12,000 39 

12,000 " 14,000 35 

14,000 " 1(),000 45 

16,000 *' 18.000 36 

18,000 " 20,000 18 

20,000 ^' 22.000 8 

22,000 •' 24.000 6 

24,000 " 26,000 7 

26,000 " 28,000 2 

30,000 " 32,000 3 

38,000 '' 40.000 3 



243 



Table XV., D. — Subacuth Articular Rheumatism. 



Age. 



9 
10 
11 
12 
13 
14 
15 
16 

17 
18 
19 
20 
21 
22 



31 



42 

26 

62 

23 
33 
36 

83 
22 
23 
31 
25 
68 
23 
13 
50 

45 
30 
15 
32 
28 
25 



M 



Red cell. 



5,040,000 
4,"75d.000 
4,430,000 



4,644,000 
3,820,000 



White 1 Percent 
cells. ' haemo- 
globin. 



39, 000 
19,200 
15,200 
26, 300 
10.000 
12.900 
84,000 
13, 600 
26, 800 
15,200 
20, 700 
13. 700 
19,500 
18,200 
18,200 
15,600 
17,500 
17.200 
16,000 
15,200 
15.000 
14,900 
14,900 
14,500 
14,200 
6,800 
13,600 
13,000 
12,000 
11,400 
10.600 
10,500 



80 



85 

"so" 



62 



60 

85 




Remarks. 



September 5th. 
7th. 
9th. 
11th. 
18th. 
22d. 
April 24th. 
" 26th. 
" 15th. 
" 17th. 
First day. 
Fourth day. 



Sixth day. 



May 24th. 

May 28th ; mitral regurgitation 



Temperature 100°. 



ACUTE ARTICULAR RHEUMATISM. 



229 



Table XV., D.— Subacute Articular Rheumatism (Gontinueci). 



6 
2 


Age. 


1 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


23 
24 
25 
26 

27 
28 
29 


33 

17 
53 
28 
? 

Adult. 

Adult. 


ii. 

F. 


4,'684,bbb 

4,016,000 
4,188,000 


10,500 
10,100 
9,900 
8,000 
7,800 
6,200 
5,750 


"es" 

75 
60 

73 


Temperature 100.5'. 



Table XV., E. — Chronic Rheumatism, Chiefly Articular. 



10 
11 
12 
13 

14 
15 
16 

17 

18 



Age. 



40 
58 
29 
75 
55 
25 
20 
33 
19 
24 
69 
78 
46 
58 
37 
32 
24 



M 



M 



Red cells. 



5,576,000 
5,"248,bb0 

4,744,000 



Average : 



White 
cells. 



13,500 

12,400 

12,400 

10,500 

10,200 

10,200 

9,800 

8,400 

8,300 

8,300 

7,800 

7,200 

7,000 

6,500 

6,500 

6,400 

6,400 

6,100 



8,660 



Per cent, 
haemo- 
globin. 



85 
67 
85 
85 
80 
62 
02 
75 
45 
67 
90 

? 

85 
60 
70 

? 

65 



Table XV., F. —Subacute Articular Rheumatism. 

White cells. Cases. 

Between 1,000 aud 10,000 17 

10,000 " 12,000... 9 

12,000 " 14,000 7 

14,000" 16,000 8 

16,000" 18,000 5 

18,000" 20,000 4 

20,000 or more 3 

Average = 11,000 -]-. 53 



230 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XV., E. "Musci i,ak liiiKUMATisM." 



No. 


Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


1 
2 
3 
4 
5 
6 
7 


46 
.52 

.54 
38 
.54 

27 

a5 


M. 

M. 
M. 
M. 
F. 
M. 


4,580,000 
4,370,0rj0 
4,300,' »00 

3,820,000 

V 

? 


7,.500 
4,(KX) 
7,.5(K) 

14,(K)0 
ti,OfKJ 
.5,r(K) 


70 
.55 
75 

? 

58 
? 
? 


During febrile attacks. 
T<nmbago. 








Average ~ 


7,328 + 







The average leiicoeytosis in the acute cases is 13,800 in those 
mild and more chronic, so-called '' suhacute,^^ cases the leucocytes 
range lower, averaging 9,760; while in chronic rheumatism, whether 
articular or muscular (including lumbago), there is no increase 
at all (average ~ 7,4-50). In acute cases the leucocytosis subsides 
with the joints, rising again if relapse or complication occurs. The 
polynuclear cells are absolutely increased with an absolute diminu- 
tion of the lymphocytes. The eosinopliiles rarely disappear as in 
most infections. After the very earliest days (when they may be 
scanty or rarely absent) they are increased despite the fever and 
exudation. In convalescence they run even higher, 13.8 per cent 
(or 970 absolute) in one of Tiirck's cases. During the fever Tiirck 
noted myelocytes and stimulation forms as in other infections. 

Blood plates are much increased during the fever. 

In 32 cases of artliritts deformans treated at the Massachusetts 
General Hospital the blood was normal except for a slight deficiency 
of haemoglobin in two cases. 

SiiUDnari/. 

Slight secondary anaemia. Anaemia with leucocytosis, the de- 
gree of which is a measure of the severity of the infection. 

Diagnostic Value. 

The blood tells us little if anything that could not be learned in 
other ways. It does not differ at all from that of septic arthritis 
or from that of acute gonorrha^al arthritis. 

The only cases that I remeUiber in which a blood examination 
has been valuable are the following : 

Case I. — The patient had muscular pains, fever, and a history 
of a malarial attack some months earlier. The question to be de- 



ASIATIC CHOLERA. 231 

cided by the blood examination was between malaria and "rheuma- 
tism." The leucocytes were 23,600 per cubic millimetre, which 
made it clear that the case was neither malaria nor "rheumatism," 
since the former never increases the leucocytes and the latter could 
give so high a count only in case genuine articular inflammation 
were present. The case turned out to be croupous pneumonia, which 
the high leucocyte count strongly suggested. 

Case II. — The patient presented symptoms and signs of acute 
polyarticular rheumatism wath fever. The fever came down under 
salicylates, but soon rose again, and the man became wildly de- 
lirious. His delirium persisted after the salicylate was stopped. 
Several joints continued swollen and tender. The fever was very 
moderate, ranging between 99° and 101°. There were no rose spots 
and no enlarged spleen. The question arose as to whether it was a 
case of sepsis with localization in the joints, or whether it was a 
case of typhoid supervening on an arthritis of some kind. The 
blood count, which was repeated several times, always showed a 
perfectly normal blood except for a slight anaemia. The subse- 
quent course of the case, during which he remained for nearly three 
weeks more or less delirious, made it clear to Dr. F. C. Shattuck, 
under whose care the patient was, that the diagnosis was typhoid*. 

Chronic rheumatism (muscular or articular) produces no con- 
stant blood changes appreciable by clinical methods (see Table 
XV.,DandE). 

ASIATIC CHOLERA. 

In no other disease, so far as I am aware, has an acid reaction 
in the blood been reported. This is at the end of life. All observ- 
ers agree that the alkalinity is at least greatly reduced. 

Our knowledge of the corpuscles is best summed up in Bier- 
nacki's ' study of 38, and Eogers - of 23 cases. 

Red Cells. — In the staduan algidum, or stage of collapse, most 
of the symptoms are due to the great concentration of the blood 
from the loss of serious fluids in the stools. Hayem found the in- 
crease of red cells from this concentration to amount to from 1,000,- 
000 to 1,500,000 per cubic millimetre. 

Biernacki^ found 7,662,500 in one case twenty-four hours after 
the beginning of the disease. The specific gravity may be as high 
as 1.071 or 1.072. 

White Cells. — Leucocytosis is present, not merely as the result 
of concentration, but as a genuine increase to at least double the 
normal count. Biernacki ^ and Rogers ^ each found that cases with 

^Biernacki: Deut. med. Woch., 1895, No. 48. 
2|^ogers: Lancet. September 6th, 1903. 



232 SPECIAL PATHOLOGY OF THE BLOOD. 

particularly high counts (20,000 to 60,000) were soon fatal, so that 
they consider a marked leucoeytosis in tlie algid stage as a bad 
prognostic sign, although patients also die with low leucocyte counts 
in this period. Thus 11 out of 11 cases with counts over 20,000 died, 
while only 4 out of 9 cases with counts under 20,000 died (Rogers). 
Such a leucocytosis does not occur in ordinary diarrhcea or dysen- 
tery. 

Leucoeytosis is present as early as twelve hours from the first 
symptom and lasts at least as late as the sixth day. In the stage 
of reaction it usually decreases. In one very mild case reported by 
Biernacki there was not only no increase, but leucopenia (4,375 per 
cubic millimetre), and Rogers noted counts of 2,000 and 4,000. 

The differential count shows usually from eighty-two to ninety- 
five per cent of polynuclcar cells and a corresponding diminution of 
the lymphocytes. Roger's figures seem to show that a large number 
of polynuclear cells (absolute and relative) and a small percentage 
(under 10 per cent) of lymphocytes means death in three-quarters 
of the cases, while more than one-half of the cases showing over 10 
per cent of lymphocytes recovered. On the other hand an absolute 
and relative decrease of large mononuclear forms was associated 
with recovery in 4 cases out of 5, while of 18 cases with over 2,000 
large mononuclear cells per cu. mm. 14 died. The eosinophiles are 
scanty. Sherrington ' found the mast cells notably increased in 
some cases. 

ERYSIPELAS. 

Ehrlich, Halla, Pee, Reinert, Rieder, and von Limbeck agree 
that leucocytosis is usually present in well-marked cases. Von 
Limbeck finds the " leucocyte curve '^ to run roughly parallel with 
the temperature chart, sometimes beginning to fall a little before 
the latter. The counts rarely run very high, yet Reinert counted 
39,627 in one case. Pee noted that the leucocyte count increases 
only while the process is spreading, and that the size of the count 
was a tolerably accurate measure of the severity of the case. 

Rieder found in seven cases an average of only 15,000 per cubic 
millimetre despite very high temperatures. In one case the leuco- 
cyte count remained high after the temperature had fallen, but in 
the others it anticipated the temperatures. In one mild case he 
found no leucocytosis. Polymorphonuclear cells are greatly in- 

' SlieiTin.^-toii : Proc. Royal Soc, 1894 p. 189. 



ERYSIPELAS. 



233 



creased as in other forms of leucocytosis. Hay em noticed the same 
dependence of the leucocyte count upon the severity of the process. 

Chantemesse and Key {Presse Med., 1899, vol. vi., p. 316) find 
that in most cases the degree of leucocytosis is parallel to the tem- 
perature curve, though the leucocytes may fall before the fever. In 
patients with average resisting power the highest counts accompany 
the highest temperature. When the area of disease extends the 
leucocytes generally rise. At the height of the fever the polynu- 
clear cells are much increased at the expense of the other forms, 
while in defervescence these conditions are reversed. 

From the third day to the end of the fever the poly nuclear cells 

steadily diminish in favorable (adult) cases. In the aged the poly- 

nuclears are especially higli, while in children the lymphocytes are 

increased, especially at the height of the process. Persistence and 

return of high polynuclear count means relapse, according to these 

writers. 

Table XVL — Erysipelas. 



Case. 


Age. 


White cells. 


Remarks. 


1 

3 


40 

38 

23 
78 
29 
51 
38 
17 
32 

V 

21 


20,000 
14,400 
14,450 
17,100 
17,300 
15,400 
16,600 
17,000 
14,000 
13,000 
12,400 
12,700 
10,300 
7,250 
6,200 


First day. 

Second day. 

Third day. 

Fourth day ; spreading. 

Temperature 105.° 


3 


4 




5 

6 




7 




8 

9 




10 

11 









In eleven cases at the Massachusetts General Hospital I found 
leucocytosis in all but three, and these were very mild cases. As 
in most infections, the usual abnormal forms (stimulation forms and 
myelocytes) may be abundant at the climax of the process. Tiirek 
records five per cent of myelocytes (320 absolute). 

When the disease occurred in " scrofulous '' cases, Hayem found 
only 7,000-8,000 leucocytes per cubic millimetre, while in cases 
with very extensive process and high fever 12,000-20,000 were 
present. He found also a loss of 500,000-1,000,000 in the count 
of the red cells, according to the severity of the case. This showed 



234 



SPECIAL PATHOLOGV OF THE BLOOD. 



itself pai'ticularly just before tlie fall of the temperature. T have 
seen no reference by other writers to the condition of the red cells 
in this affection. 

TONSILLITIS (FOLLICULAR). 

Halla', Pick,- and Pee ^ found leucocytosis as a rule in uncom- 
plicated follicular tonsillitis; Riedei' found it in a case complicated 
with acute nephritis. 

The following table confirms these observations in the main, 
though in mild cases no leucocytosis was present. 



Table XVII. — Tonsillitis. 









1 

1 Whitp 


Per cent 






Age. 


X 


Red cells. 




haemo- 


Remarks. 


z 




^. 






globin. 




1 


19 






41,000 


90 


Temperature 102.2 (acute). 


2 


20 






36,000 


85 


Temperatuie 102.8 (acute). 


3 


2 

■ ■ 







34,400 
26,900 
26,300 


.... 




4 


2 






28,100 


85 




5 


7 






28,000 






6 


29 






23,400 


85 


Acute follicular. 


7 


3 







23,300 
12,400 


60 


July 7th. 
July 9th. 


8 


23 


_ 





23,100 
7,600 




Dec. 24th. FoUicular. 
Dec. 26th. 


9 


19 







22,600 
14,500 


80 


Acute folhcular. Nov. 1st. 
Nov. 3d. 


10 


21 






21,700 


62 


Acute follicular. 


11 


18 






21,200 






12 


22 






21,000 
18,000 


90 


Feb. 2d. Acute. 
Feb. 8th. 


13 


22 


F. 


4.368,000 


19,200 


35 




14 


22 






18,500 


. . . 




15 


27 






18,200 


100 




16 


26 






18,100 


.... 




1^ 


21 


F. 




18,000 






18 


24 






18,000 


.... 


Acute follicular. 


19 


27 


M. 




18,000 






20 


20 






17,500 


75 




21 


37 






17,400 


75 




22 


12 




^ 


17,300 




Streptococcus. 


23 


28 




. . . . r . . . 


17,000 


95 




24 


23 






16,800 






25 


21 


F. 




16,800 




Acute follicular. 


26 


25 


F. 




16,200 






27 


30 


F. 


4,750,000 


16,000 


80 


Temperature 101. 


28 


28 






16,000 


80 




29 


24 







16,000 








'Zeitschrift f. Heilk., 1883, p. 198. 
'^Prag. Med. Woch., 1890, p. 308. 
'Pee: Inaug. -Dissert. , Berhn, 1890, p. 8. 



TONSILLITIS. 



235 



Table XVII.— Tonsillitis {Continued). 



30 
81 
32 
83 
34 



Age. 



27 
32 
24 
16 
43 



M. 



35 


Adult. 


36 


17 


37 


30 


38 


24 


39 


Adult. 


40 


24 


41 


36 


42 


24 


48 




44 


28 


45 


24 


46 




47 


19 


48 


18 


49 


26 


50 


24 


51 


23 


52 


22 


53 


18 


54 


22 


55 


27 


56 


24 


57 


16 


58 


38 


59 


23 


60 


34 


61 


45 


62 


19 


63 


Adult. 


64 


27 



F. 



Red cells. 



4,860,000 

4,730,666 
5,000,000 



4,952,000 

5,816', 666 

I 5,000,000 
4,552,000 

5,150,000 



F. 



5,016,000 



4,200,000 



White 

cells. 



15,500 
15,000 
14,800 
14,400 
14,200 
14,600 
14,400 
16,800 
14,000 
14,000 
13,500 
13,500 
135,000 
13,300 
13,200 
13,200 
12,250 
12,000 
11,900 

11,800 
11,600 

11,500 

11,000 

11,0(jO 

10,900 

10,500 

10,000 

9,600 

9,200 

8,200 

9,100 

9,000 

8,800 
7,925 

7,700 
6,800 
6,500 
5.800 
5,800 



Per cent 
haemo- 
globin. 



67 

166' 

80 
90 



80 
76 
68 



90 
94 

'65' 

90 
65 

83 

65 
68 
90 

80 

"86' 

65* 
70 

70 
52 



90 
60 

85 



Remarks. 



Six days ; slight. 

Acute follicular. 

August 1st. 
August 5th. 
August 8th. 
August 8th. 
Follicular. 
Acute. 

Convalescent. 
Follicular. 



Follicular. 

Acute. 

Streptococcus ; slight articu 

lar rheumatism. 
Follicular. 
Temperature 104.3. Aortic 

Regurgitation. 
Chronic recurrent, out in two 

days. 

Follicular. 



August 12th. 

August 14th. 

Temperature 102. Follicular. 

Temperature 100.4. Follic- 
ular. 

January 15th. Follicular. 

Follicular; slight; tempera- 
ture 99" next day. 

Bronchitis. 



Follicular. 
Follicular. 



At the close of the attack a slight eosinophilis has been noted 
by several observers. 

The blood examination has no diagnostic value so far as I am 
aware. It is worth knowing that a simple tonsillitis can cause 



236 SPECIAL PATHOLOGY OF THE BLOOD. 

leucocytosis, to the end that if such is discovered on blood exanuna- 
tion we need not suppose that some other process is present to 
account for the increase. 

GRIPPE. 

" Grippe " is a term very loosely used to designate any infection 
of relatively short course, especially if catarrhal symptoms are pres- 
ent. Seldom is the diagnosis established by satisfactory bacterio- 
logical evidence. In all probability; therefore, many of the cases 
included in the table below are not true "influenza." 

The references to the haematology of the disease in literature are 
very scanty. Orion (A'rchiv. d. IlecL in Hit., 1890, p. 280) found 
fibrin increased during the early days of the disease. Kieder 
(Munch, vied. Woch., 1892, xxxix.) found no leucocytosis in grippe 
and but little in the "catarrhal pneumonia" following it (Tiirok). 

Blum (Wien. klin. Woch., April 13, 1899), found normal or sub- 
normal counts, the latter especially in the '• abdominal " type of the 
disease. Gerber (ibidem, 1900, Xos. 25-27) and Stengel report 
figures much like mine, i.e., rarely over ir),000 per cu. mm. 

The following table shows that the leucocytes are normal in 
about two-thirds of the cases. One hundred and seven of the three 
hundred and nine cases showed leucocytosis, but in several of these 
some complication was very possibly present. Only 34, or 11 per 
cent, showed over 15,000 leucocytes. The absence of leucocytosis is 
of importance in Q^GhxHmg jmeuwonia and local in-flamii)atory cow- 
ditions. The leucocyte count does not help us to distinguish the 
disease from typhoid. In this decision the serum reaction is our 
mainstay (see page 529). From malaria it may be distinguished 
by the absence of malarial organisms. In one case, after an oper- 
ation for traumatic epilepsy, the temperature rose to 104^, with a 
chill, and the question of meningitis was considered. The absence 
of leucocytosis excluded the meningitis, and the attack turned out 
to be grippe, which was just then very prevalent. 

Table XVIII. -Grippe. 

White Cells. 
Between 2,000 and 3.000 = 3 cases. 
3,000 *' 4,000 = 8 " 
4,000 •' 5,000 = 15 " 
5,000 •' 6,000 = 32 " 



SEPTICEMIA. 237 

Table XYIII. — Grippe {Continued). 

White Cells. 
Between 6,000 aud 7,000 = 40 cases. 



7,000 '• 


8,000 


= 25 


8,000 '• 


9,000 


= 28 


9,000 " 


10,000 


= 33 


10,000 '^ 


11,000 


= 27 


11,000 " 


12,000 


= 24 


12,000 " 


14,000 


= 83 


14.000 " 


15,000 


= 17 


15,000 " 


16,000 


= 10 


16,000 " 


17,000 


= 7 


17,000 " 


19,000 


= 5 


19,000 '•' 


20,000 


= 6 


20,000 " 


21,000 


— 2 


21,000 + 




4 




Total = 


-- 309 



Red Cells. 
Between 3,000,000 and 4,000,000 = 3 cases. 
4,000,000 " 5,000,000 = 10 " 
5,000,000 " 6,000,000 = 15 " 

28 " 

SEPTICAEMIA. 

Puerperal septicsemia, infected wounds, septic arthritis, septic 
endocarditis, general infections wdtli pyogenic bacteria, "pyaemia,'' 
are all identical so far as their effects on the blood are concerned, 
and Avill be considered together under the general head of Septi- 
csemia. 

Bacteriology of the Blood. 

Cocci can be demonstrated in cultures from the blood of septi- 
caemia more frequently than in any other class of infections. Eo- 
senbach ' in 1884 found stre^Dtococci and staphylococci in sepsis. 

Garre - in 1885 found the last-named coccus in a case of osteo- 
myelitis. Ill 1890 V. Eiselsberg ^ found staphylococci in ten cases 
of septic wounds and one case of osteomyelitis, and streptococci 
and staphylococci together in five more patients whose wounds had 
become septic. 

^ " Microorganismen b. d. Wundinfectionskrankheiten," etc. Wiesbaden, 
1884. 

2 Fortscb. d. Med., 1885, Ko. 6. ^ ^yien. \^\\^^ Wocb., 1890, No. 30. 



238 SPECIAL PATHOLOGY OF THE BLOOD. 

Czerniewsky,^ Steriij and Hirseliler'- found the .same organisms 
in puerperal fever, the former observer in five cases. 

Brunner/ Hoff/ and Bhim '" found })yogenie staphylococci in 
pyaemia and sepsis, and Saenger," Eoux and Lannois,MJantu ® an*! 
Bommers^ had equal success, each in a single case. 

Canon ^" and Sittman^^ investigated large numbers of cases with 
many positive results, and Grawitz '^ and Petruschky '^ and Cohn " 
were successful in finding pyogenic cocci in the blood of cases of 
ulcerative endocarditis as well as in other septic infections. Her- 
schlaff'" found them in erysipelas, acute tuberculosis, perforated 
typhoid ulcer, etc. Kuhnau,""' on the other hand, was unable to find 
anything in the blood of twenty-three severe pysemic cases, and was 
successful in only one out of twelve cases of ulcerative endocarditis. 

Taking the results of all these investigators together with those 
of White,'' Krauss,'" James and Tuttle,'" Brieger'^" and Neumann,-' 
we get a total of 316 cases, wdth 107 positive results, or 33 per 
cent. I agree with Da Costa that these figures give too favorable 
an impression as to the value of blood culture in sepsis. Still 
Grawitz insists that if we are not content with a single trial in 
negative cases, the majority of eases show the presence of pyogenic 
organisms, and that in obscure se^^tic cases the diagnosis ma}' be 
greatly facilitated by such an examination. Negative results are 
of course very far from excluding septicaemia, but positive ones are 
sometimes of great value if proper precautions are taken in the 
technique of the examination. In the diagnosis of malignant endo- 
carditis, often a most difficult one, Grawitz thinks blood cultures 
are especially important and likely to prove positive when the dis- 
ease is present (see Diseases of the Heart, p. 346). 



^ Archiv f. Gynakol., 1888, No. 33. '^ Deut. med. Woch., 1897, No. 9. 

2 Wien. med. Presse, 1888, No. 28. ''' Sem. Med., 1897, p. 105. 

^> Wien. Win. Woch., 1891, No. 20. "^ Dent. med. Woch., 1897, No. 2-5. 

•^Dissert, Strassbm-g, 1890. '• White: Jour, of Exp. Med. 1889. 
5 Milncb. med. Woch., 1893, No. 16. vol. iv., p. 425. 

« Deut. med. Woch., 1889, No. 8. ^^ Krauss: Zeit. filr Heilk., 1896, vol. 
'' Revue de Med., No. 12. xvii., p. 117. 

^ Rif. Med., 1892, No. 96. '^ James and Tuttle : Report of Pres- 
9 Deut. med. Woch., 1893, No. 16. byterian Hosp., 1898, p. 46. 

^c Deut. Zeit. f. Chirrug., 1893, p. 571. -"^ Brieger: Charite-Annalen, 1888, p. 
^' Deut. Arch. f. klin. Med.. 1894, p. 573. 198. 

^- Charite-Annalen. 1804, vol. X. -'Neumann: Berl. klm, AYoch., 
''' Zeit. f. Hygiene, 1894. pp. 59 and 413. 1888, vol. xxv., p. 143. 



SEPTICEMIA. 239 

Almost all observers agree that tlie finding of pyogenic cocci 
(except the staphylococcus albus) in the blood makes the prognosis 
almost surely fatal. The toxicity of the blood is doubled. 

Red Cells. — All observers agree that very marked anaemia is 
present in severe cases. Ked marrow post mortem I have seen in 
two instances. Roscher's ^ investigations tend to show that the 
diminution in red cells in septicaemia is greater than in any other 
infective disease, and appears in a shorter time. He found such a 
diminution present no longer than a fev/ hours from the beginning 
of the illness. He finds the amount of anaemia proportional to Ww 
severity of the case, and (reckoning by means of the estimated solid 
residue) concludes that whenever the blood has lost one-quarter of its 
substance or more, death follows. He considers, therefore, that help 
as to prognosis is given us by the blood examination in septicaemia. 

The serum becomes very watery, partaking of the general atro- 
phy of the blood tissue. In a case of intensely acute puerperal 
sepsis, with profuse uterine bleeding, Grawitz found the red cells 
reduced to 300,000 (!) although the patient had been sick less than 
twenty-four hours. The case seems almost incredible, but is re- 
ported in great detail in the author's recent text-book, to which 
reference has so frequently been made. He accounts for it by the 
combination of haemolysis and dilution. 

In eleven cases of puerperal sepsis seen at the Massachusetts 
General Hospital in recent years the red cells averaged 3,500,000, 
which is very low, considering the shortness of the illness in most 
cases. (The influence of hemorrhage during parturition must of 
course be taken into accouirt.) 

In most of the septic wounds which I have seen the counts have 
not been low. But in one case of septicaemia from a suppurating 
fibroid of the uterus the red cells numbered only 1,800,000. Ewing 
reports a septic endometritis Avith 1,600,000 red cells. In a case 
of puerperal sepsis of only a few days' duration, in a woman not 
previously anaemic, Hayem ^ recently reports the following figures : 

December 3d— Red cells 1,450,000 

White cells 7,500 

Haemoglobin 20 per cent. 

December 6tli— Red cells 2,578,000 

White cells 8,000 

Haemoglobin .... 40 per cent. 

^ InauiT. Dissert., Berlin, 1894. - La Med. Modernc .Jainiaiv 13th. 1897. 



240 SPECIAL PATHOLOGY OF THE BLOOD. 

December 24th— Red cells 4,231,000 

White cells 7,200 

Haemoglobin 65 per cent. 

(Recovery.) 

Such cases are the best examples we have of an (icnti- ancemia 
(hemorrhage excepted). 

The hcemorjlohin is usually diminished uljout as uuich as are the 
corpuscles. 

Nucleated red cells are very often seen; whether or not they 
have prognostic value cannot yet be stated, in differential diagno- 
sis their presence helps us to exclude typhoid and miliary tubercu- 
losis, in which diseases they rarely are found. 

Table XIX, — Plekpeual feEPTiCiEMiA, 











Per cent 




o 


Age. 


Sex. 


Red cells. 


White cells, haemo- 


Remarks. 


!z; 








1 globln. 




1 


31 


F. 




77, 500 




Autopsy. 


2 


21 


F. 


2,300,000 


26,000 






3 


29 


F. 


3,900.000 


23,900 

21,000 

9,500 

15,500 

15,000 


68 


Two days before delivery. 

Day of delivery. 

One day after delivery. 

Five days after delivery; 

breasts caked. 
Ten days after delivery. 










11.800 ! .. 


Twenty-six days after delivery. 


4 


28 


F. 


3, 784, 000 


22,000 

13,600 

8,300 


55 


Miscarriage five days before ; 

septic ; curetted. 
Three days later, temperature 

falling. 
Seven days later, temperature 

normal. 
Fourteen days later, tempera- 










15.800 
















ture up ; curetted again. 










14,900 




Fifteen days later, temperature 
falling. 










15,000 




Sixteen days later, temperature 

falling. 
Thirtj'-two days later, temper- 










9,500 










1 


ature falling. 


5 


25 


F. 





20,800 1 55 




6 


34 


F. 




15,900 i .. 


September 2d, 1897. 




1 


35,600 


September 9th, chillg. 










33,000 


_ 


September 13th. 










35.600 




September 1 6th. Recovered . 


7 


25 


F. 


2,936,000 


20,000 
21,090 


50 


April 1st. 1894. 
April 3d, 1894. 


8 


32 


F. 


4,904,000 


19,300 
9,300 




Curetted. 

One week later, welL 


9 


24 


F. 


3,556,000 


18,400 






10 




F, 




Marked 
increase 


•• 


Polymorphonuclear cells, 94^; 
lymphocytes, 6^. 



SEPTICEMIA, 



241 







Table XIX 


—Puerperal Septicemia {Continued). 












Per cent 




. 


Affe. 


Sex. 


Eed cells. 


White cells. 


haBmo- 


Remarks. 


z 










globin. 




11 


26 


F. 


5,368,000 


5,600 




Died. 


12 


24 




3,428,000 


33,500 

28,800 


45 


With general peritonitis. 
Secondary operation. 


IB 


19 




3,536,000 


9,600 
6,800 




July 18th. Pelvic cellulitis. Diff. 
count 500 cells (chlorosis). 
Poly nuclear, 73^ ; lympho- 
cytes (s.), 22; lymphocytes 
(1.), 4 ; eosinophiles, \%. Reds 
slight irregularity in size and 
shape. No nucleated reds seen. 

July 29th. 


14 


23 




4,400,000 


14,500 
13,400 

7,400 
17,500 
12,200 

9,300 


45 


May 2d. With toxic nephritis. 

May 9th. 

May 14th. 

May 24th. 

May 28th. 

June 3d. 


15 


26 




4,056,000 


12,400 

14,800 
18,400 


30 


June 8th. Secondary anaemia. 
Polynuclear, 86.6^ ; lympho- 
cytes (s.), 9.4%' ; lymphocytes 
(1.), 3^ ; eosinophiles, .8^; my- 
elocytes, .2%. Reds stain 
palely in centres, moderate 
poikilocytosis and irregularity 
in size. Normoblasts, 1. 

June 14th, 

June 28th. 


16 


27 






12,200 

8,200 

11,400 




December 5th. 
December 9th. 

December 11th, died. P., 140- 
170; T.,103°-105°;R., 35-60. 


17 


40 






9,200 




T. 104°. Recovered. 


18 


38 


F. 




23,400 
13,600 
15,200 
14,900 
8,400 
16,200 


75 


Jan. 22d. 
" 23d. 
" 24th. 
" 25th. 
" 27th. 
•' 29th. 









Table XX., 


A.— Septic Wounds. 


d 


Age. 


1 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 
2 
3 

4 
5 


37 
28 
31 

37 


F. 
M. 
F. 

M. 
M. 


5.880,000 
7,600,000 
5,680,000 

5,840,000 
4,450,000 
5,600,000 


48,400 
25,400 
15,300 

23,200 

10,500 

8,800 




Sloughing breast ; bedsore. 
Septic wound of foot. 
Sloughing breast after cancer 

operation. 
One month later ; wound clean. 
Septic hand. 
Septic finger. 



16 



242 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XX., B. — Septicemia with Arthritis. 











Per cent 




1 


Age. > 




< Red cells. 


White 
cells. 


haemo- 
globin. 


Remarks. 


1 


8 -^ 


I 


25,000 
43,000 

24,000 

20. 700 

6,700 




Pus in elbow joint : no injury. 
Two days after operation, vent 

not free ; opened further. 
Seven days after operation. 
Eight days after operation. 
Sixteen days after, well. 


2 


21 




23,800 




T. 101°. 


3 


34 B 


I 


19,000 


65 


Gonorrhoea! pus in knee. 


4 


59 ^ 


I. 4,520,000 


18.500 




Pus in shoulder joint ; no trauma. 


5 


28 




18.200 




T. 99°. 


6 


22 




17,500 


72 


Gonorrhoea and syphilis. 


7 


55 




17,500 




Gonorrhoea]. 


8 


? 




17,100 




Gonorrhoeal. 


9 


28 




16,500 




Gonorrheal. 


10 


42 




14,100 


50 


Gonorrhoeal. 


11 


22 




13,800 




Gonorrhoeal ankle. 


12 


16 




13.300 


52 


Gonorrhoeal. 


13 


32 


. 3,864,666 


12.500 




T. 99°. Gonorrhoeal. 


14 


32 




12.200 




T. 102°. Gonorrhoeal. 


15 


33 




11.900 




Gonorrhoeal. 


16 


32 




9,700 




T. 101°. Gonorrhoeal. 


17 


21 




9,400 




Gonorrhoeal. 


18 


28 




9.100 




Gonorrha?al. 


19 


28 




9,000 




Gonorrhoeal. 


20 


39 -^ 


I 


8,940 




Ankle gonorrhoeal. Cultures neg- 
ative. 


21 


? 




8,800 


76 


Gonorrhoeal. 


22 


32 




6,200 




T. 101 \ Gonorrhoeal. 


23 


21 . 





6,200 




Gonorrhoeal. 



Table XX., C— General SEPTic^isnA. 





Age. 


>i 


Red cells. 


White 
cells. 


Per cent 
haemo- 


Remarks. 


^ 




^ 




globin. 
















fTemp. 104°. 
1 Pulse, 92. 
1 Apex 220. 
Cardiac dilatation. Death, 


1 


36 






62,900 


90 














2 


Adult. 


M. 


5,248,000 


41,400 






3 


a 


F. 


1,800,000 


46,000 





Suppurating fibroid. Strepto- 
coccus. 


4 


23 


F. 


3,776,006 


25,800 


52 


A fatal case, yet no fever.' Strep- 
tococcus. 


5 


65 




" 


25,200 
24,900 
20,400 
28.600 
31,700 


65 


June 30th. 
Juue 30th. 
July 1st. 
JulV 3d. 
July 4th. 



SEPTICAEMIA. 



243 



Table XX., C. — General Befticmmia {Coiitinued). 













Per cent 






Age. 


X 


Red cells. 


White 


haemo- 


Remarks. 


^ 




^ 




cells. 


globin. 












24,800 
23,500 
24,000 




Jul}^ 5th. 
July 6th. 
July 8th. 
June 30tli. Differential count, 

400 cells. 
Polynuclear, 86. 
Small lymphocytes, 5.5. 
Large lymphocytes, 8. 
Eosinophiles, 0.5. 


6 


44 


• ■ 




20,700 
30,700 




Cholangitis. 

Pus in eye and throat. Strepto- 
coccus. 


7 


43 







12,100 




Cause? 


8 


20 






27,000 




Septic leg, pus burrowing. 


9 


11 






10,800 
13,000 
18,600 
19.400 
13,200 
12,200 
12,400 
10,400 
11,000 
22,000 
34,000 




December 15th. 
December 17th. 
December 19th. 
December 20th. 
December 21st. 
December 23d. 
December 23d. 
December 28th. 
January 5th. 
January 15th. 
January 19th. Autopsy. 


10 


33 






24,000 
19,400 
18,000 
19,600 
43.200 


75 


April 24th. 
April 26th. 
May 1st. 
May 3d. 

May 11th. T. 104f°. No au- 
topsy. 


11 


55 






10,100 




Pneumococci in blood. Autopsy. 


12 


33 




4,160,600 


22,000 

16,000 
22,000 


45 


Multiple septic embolism. Sugar 

in urine. 
Tenth day. 
Seventeenth day. Autopsy. 


18 


38 






19,800 
29,100 
27,200 
25.200 




First day. 
Third day. 
Fourth day. 
Sixth day. 



Deformities in the shape and size of the corpuscles are not usu- 
ally marked except in the severest cases. Ewing has noted a reduc- 
tion in the diameter of the cells in anaemic cases. 

Hcemoglohincemia with reddish staining of the serum is often 
noticeable in the dried and stained cover-glass specimen when the 
plasma is deeply stained. 

Leucocytes. — Considerable controversy has taken place as to the 



244 SPECIAL PATHOLOGY OF THE BLOOD. 

changes in the white cells in puerperal septicaemia; some observers 
linding leucocjtosis, while others find none. 

The results of experimental infections referred to al>ove 
(see page 102) and the parallelism of the leucocyte changes in 
pneumonia, peritonitis, and diphtheria fully ex^dain these ap- 
parent divergences, which })erfectly excm])lify the rules stated on 
page 97. 

Leucocytosis occurs onh* when the struggle between tlie patient 
and his disease is intense, and whichever is victorious. When 
either side wins without any difficulty, if., in the mildest and in 
the severest cases, leucocytosis is nearly ov entirely absent; indeed, 
leucopenia may be found (as for instance in a case of septic endo- 
metritis reported by v. Limbeck — only o,000 leucocytes). Von 
Limbeck and Krebs ^ fonnd no leucocytosis in cases of puerperal 
septicsemia, but these were all fatal cases or very mild ones. Eie- 
der, on the other hand, and the great majority of other observers 
(Sadler,^ Eoscher,^ Kanthak,' Grawitz, etc. ) find leucocytosis. This 
means that in most cases observed by these writers the infection was 
of moderate severity. Ewing's experience leads liini to the conclu- 
sion that while the rule that suppuration produces leucocytosis is 
almost invariable, it must be remembered that leucocytosis may 
promptly disapx^ear when exudation ceases, and that suppura- 
tion involving mucous surfaces may induce very slight leuco- 
cytosis. 

Onl}' 14 of the 56 cases in Tables XIX. and XX. showed no 
leucocytosis. One was very mild, the othei- proved fatal on the 
day of the count. The leucocytosis is of the ordinary polynuclear 
type with disappearance of eosinophiles and diminution of lympho- 
cytes. Myelocytes and ''stimulation forms" are usually present in 
small numbers. lodophilia is always marked, and may be of value 
in the diagnosis of cases with leucopenia. The reappearance of the 
eosinophiles seems to me to have some favorable prognostic signifi- 
cance. 

'Krebs: Dissert., Berlin. 1893. 

2 Sadler: Loc. ci't. 

^Roscher; Dissert., Berhn, 1894. 

^ Kanthak : Brit. Med. Journal. June, 1893. 



PPENDICITIS. 245 



Si(iniiinrij. 

1. Eapid development of severe anaemia. 

2. Leiicocytosis marked, exeei)t in very mild or very severe 
cases. 

3. Blood cultures may contain pyogenic cocci. 

Diagnostic Value. 

The advantage of a positive bacteriological examination is obvi- 
ous. Of the value of the blood count in distinguishing septic from 
non- septic wounds and estimating the degree of sepsis and the im- 
portance or needlessness of ox)erative interference a great deal has 
been written within the last three years. The question will be 
thoroughly discussed in connection with appendicitis (see page 
249). 

Local Suppurative Process. 

The effects of abscess upon the blood are, I suppose, due to sep- 
ticaemia. Nevertheless septicaemia icith abscess formation differs 
enough from septicaemia u-itltout abscess formation, both clinically 
and haematologicall}', to make a sepi.rate description convenient. 

The most easily studied variety of abscess is that connected witli 
appendicitis, inasmuch as the frequency of operations in such cases, 
gives us opportunity to verif}^ what we suppose to be indicated by 
the blood count and see Iioav far our suppositions are true. 

At the Massachusetts General Hospital, most patients with other 
varieties of abscess go straight to the surgeon and their blood is not 
examined, but many cases of appendicitis come first to the medical 
wards, and hence we have records of nearly one thousand cases 
whose blood has been examined. 

I shall therefore begin the description of the blood in abscess by 
an account of appendicitis, which may probably be considered a 
typical case of abscess formation. 

APPENDICITIS. 

In the following table I present a small group of the Massachu- 
setts Hospital cases, which represents fairly well the conditions 
found in averasre cases : 



246 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXI— Appendicitis. 



-=^ 


1 





■— 













■Sa' 


.^i2 


S2.3 


Remarks. 


6 


< 
48 


1 


«s 


Si 


|5t 




1 


M. 


3,400.000 


52.000 




Question of typhoid : pus found at operation- 


2 


40 


M. 


6,800,000 


43,000 




Chrome case; 96 per cent, of polvnuclear leuoocvtes. 


3 


30 


F 




39,900 






4 






5,184,000 


36.h00 






5 






4,800.000 


36,000 






6 


50 


M. 


4.290.000 


35,000 












6,000.000 


34,000 





Three days after operation. 


fi 






6,500,000 


34,000 




Seven 


^ 


•> 


M. 


5,072,000 


28,000 






10 








24.200 





Second attack: operation at 11 p.m. November 5th, 










count at 5:30. 










16.850 




Serous peritonitis found. November 6th, 5 p.m. 
November 7th, 3 p.m. 










15.0IW 












10.r«H) 




8th, 4 " 










15.100 




Temperature still up. November 9th, 5 p.m. 










14,600 




November 10th. 5:30 p.m. 










11,800 




11th, 8:30 " 










17,850 




12th, 8:30 " 










18.200 




13th, 8 a.m. 










13,100 





13th. 8:30 P.M. 
Recovery complete ten days later. 


11 








24,000 


24° September 1st; operation, free turbid fluid without 








' 






adhesions. 










12,500 




September 10th. 










19,.500 




12th ; pocket of pus found. 


1-2 


23 


M. 


5,200,000 


24,000 






13 






5,144,000 


23,000 
16.100 


82 


January 14tli. 

15th: before operation, 1 v. + pus. 


14 




M. 




22,500 


Not operated: entrance. 










13,000 


Second dav. 










9,.500 


iThird 


15 




M, 




22.300 


12 : 20 operated : belly full of pus. 










9.500 




8 : 30 moribund ; blood dark and hard to get. 


16 


35 


F. 




22,0(10 
19,100 


. . i ° 


July 6th. 






" 8th. 










14.900 




" 10th, T. 104° : recovery. 


17 




M. 




21,900 





Appendicitis eight to nine days; operation; post-caecal 
abscess. 


18 








21,700 




November 5th. first operation. 










21,401) 




lOtli. 










16,000 





13th. 










24.400 




" , 1.5th. 










20,200 




16th. 










47,700 





" 19th, second operation (pus pocket). 










16,700 




20th. 










13,000 




21st. 










10,700 




22d. 










30.300 





26th, third operation (pus pocket). 










20,900 





27th. 










17,700 




28th. 










25,100 




29th. 










28,100 


; " 30th. 










20,400 


iDecember 1st. 










15,400 


" 2d. 










25,000 




3d. 










11,900 




4th. 










15,600 




5th. 










21,900 




6th. 










19,000 




7th. 










11,900 




8th. 










12,800 




9th. 










11.700 




10th. 










12,300 




11th. 










15,600 




12th. 










18.400 





13th. 










14,700 




21st. 










16,500 




25th. 










11,300 




" ' 26th 


19 


|81 


M. 




20,540 


1 


October 5th. 



APPENDICITIS. 



247 



Table XXI. — Appendicitis {Continued). 









•d.2 


1^ 


cent 
nio- 
bin. 


Remarks. 


z 


Si 




tf8 




l-*-S 




'Q 


31 


M. 




33,000 
14,640 




October 6th. 






8rh. 








9,800 


" 9th ; moved bowels. 








21,000 




12th : tentler still aud tense. 








24,900 




99° to 100° temperature. 








13,700 




Normal: still sore. 


>0 




M 






Appendicitis twenty-four hours; resistant belly. 
October 23d. 








20,100 










14,000 




24th. 9 a.m. 








12,400 




24th, 4 p.m. 










13,250 




24th. 11 P.M. : not operated. 










8,750 




" 85th, 8 a.m.: liquids every two hours. 










9,600 




85th, 3 p.m. 


?1 


•^4 


F. 


20,000 
19,000 




May 84 th. 
" 85th. 












'i2 


■• 


. . . . 


■ " 


20,000 
9,000 
10,000 




June oth : temperature, 101.4°; pain and vomiting. 
June 7th: no pain. 

" 8th; no pain; temperature, IOO.60; discharged. 


2:j 




.. . . 


4,800,000 


20,000 




Operated; pus. 


■M 






5,564,000 


20,000 






2b 







4,670.000 
5,896,000 


19,750 
15,000 




January 13th. 
1.5th. 


ye 


80 


h\ 


'4,680,00b' 
4,688,000 


19,600 
12,000 
8,933 


•• ••• 


" 29th. 
February 1st. 

5th; after operation. 


Jir 








19,500 




No operation. 
Purulent peritonitis. 


88 


58 


M. 


5,180,000 


19,000 




89 


80 


M. 


5,680,000 


18,930 






M(l 


14 


IM 




18,000 
17 500 






^1 










Accident case; operation; pint of pus under pressure. 
Fifth day. November 7th. 


38 


35 


M. 




16,'250 













17,450 




November 8th. 










12,000 




11th; not operated; well on 17th. 


3:^ 


85 


M. 




16,800 






84 








16,200 
16,051 




Eighth day; operation; large abscess cavity. 

Operated. 
Entrance. 


85 


40 


F 






36 








16,000 












8,000 




Same evening; no operation 










7,500 




Next daj'. 










6,800 




" " 


37 




... . 


6,160,000 


16.000 




General peritonitis. 


3^ 








16,000 
8,000 





November 12th, noon 










12th, 8: 30 P.M. 










7,500 




" i;3th, 8 A.M.: not operated. 










6,600 




13th, 8 P.M. 


39 






3,300.000 


16,000 






40 


17 


M. 


4,380,000 


15,600 
19,500 

22,900 
35,300 


66 


March 25th, 9 p.m. : vomiting, pain, tenderness. 

27th ; comfortable, no vomiting; signs more 
localized. 
" 28th : slight tenderness only. 
" 89th ; bowels move well; no symptoms. 
" 30th ; operation; large amount of pus. 










38,800 




41 


87 


M. 


4,330,000 


15,523 






48 


83 


M. 


5,910,000 


15.330 






43 


88 


M. j.... ...... 


14,800 
10,000 




20th ; general peritonitis. 

21st ; 


44 








14, 700 




Five days ; third attack: operation; free turbid fluid, 














no perforation ; prompt recovery. 


45 


36 


J^'. 


4,250.000 


14,700 
13,150 


70 


27th, 8 P.M. 

28th ; symptoms less ; no operation. 


4H 


83 


h\ 




14,400 
10,300 




February 23d, ^ 5 j-j. foul pus. 






47 




.... 


4,950,000 


14,000 




Catarrhal. 


4K 








13,400 
11,800 




3 P.M. , November 9th: appendicitis twenty-four hours. 
5 P.M., November 10th: temperature, 98.8°. 






- 






49 




. . . 


5,000,000 


13,000 






50 


•• 


....j 1 13,000 

1 1 17.000 




Visible tumor. March 27th. 

April 26th, operated; pus. 


bl 






i 4,686,000 


. 12,000 







248 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XXI. — Appendicitis (Co/dijiued). 









-s-s 




III 


Remarks. 


6 


^ 

<; 


1 


tfS 


^^ 


|lu 




52 


M. 




12,000 




Appendicitis cake. August 3d, operation: gangrenous 












1 appeudix with adhesi<jti.s. 










16,900 


August 6tJi, faecal llstula. 


^8 




M 




11,900 














operated. 


M 


.•M 


M 




11,800 


. 


Very slight tenderness; no resistance or dulness. 










19,900 





July 6ch. 
Temperature up: tenderness and resistance. July 7th, 
operation: pus found. 










1 1 ,700 


58 


December Ji8tli, 4 p.m. 


5r. 




M. 


4,860,000 


17,600 
16,670 
11,950 
10,800 
10,875 







30tli, 10 a.m. 

31st. 11 " 
Jauuary 1st, 9 p.m. 

5tli. 
July 27th; nine days pain and vomiting. 


5c. 




h\ 


4,664,000 


21,000 
10 700 





July 2bth: more pain, tenderness and vomiting; opera- 
tion showed pus. 
November 7th, appendicitis six days. 


5V 




M. 





9.000 
10,500 





Operation: abscess with considerable pus; gangrenous 

perforated appendix with concretion in it. 
Not operated till later. 


58 


I5i 


1^'. 


3,690,000 


10,400 




February 6th. 12 m.; slight pain and tenderness. 


fi'l 


4H 


IM 




9,800 




7th, 3 P.M. ; temperature dropping. 
Catarrhal. 










10,400 





60 


•• 




5,600,000 


10.500 
10,140 





One week, fourth attack: no cake, no acute symptoms; 


fil 




M 








operation: no pus. 
Sixtli dav, operation : abscess, I i. pus. 










10,040 




62 




M. 




9,000 





Operated: no pus: catarrhal 


6S 




M 




H 400 




De'^ember 1st 


W 


24 


F 




10,000 




6th. 










7,200 




15th. 










7,600 




16th. 










7,700 





No pus. 


65 




. . . . 


5,106,000 


7,600 






66 




.... 


5,600,000 


7,600 





No operation. 


6/ 






6,500,000 


7,600 




No pus. 


08 






6,500,000 


7.050 




Catarrhal appendix; five days in hospital 


6y 


ki 


M. 




7,000 


85 


Catarrhal appendix. 


70 


47 


M. 


6,000,000 


6,800 




chronic; nearly well; operation; no pus. 


7' 


'SH 


IM 




6,000 




" or verj' slight. 


72 


•22 


F. 


4,320,000 





From the seventy-two cases of tlie adjoining table, together with 
about six hundred other counts not here recorded, the following 
conclusions are to be drawn: 

1. Red cells: no changes except in chronic cases with long- 
standing abscess. 

2. Coagulation often slow, but libriii always increased in sup- 
purating cases. 

3. As in most infections, the mildest and the severest cases 
show no leucocytosis. Six cases icltlt general purulent jperitonitls 
showed no leuGocytosisj its absence being confirmed by repeated ex- 
aminations. The total absence of leucocytosis in a case not obvi- 
ously mild is a very bad prognostic sign as in pneumonia and 
diphtheria. 



APPENDICITIS. 249 

4. Catarrhal appendicitis is rarely accompanied by leucocytosis 
(only once in this series — 14,000). In Da Costa's 38 cases of " ca- 
tarrhal and interstitial" appendicitis there were but four with 
counts above 15,000. 

5. An increasing leucocytosis means a sp reading process anO mag 
he tlie only evidence of the fact. In Case 40 of this series, the pa- 
tient entered with vomiting, localized pain and tenderness. The 
leucocytosis was 15,600. Three days later he was comfortable, 
had no vomiting and very little tenderness, and in all respects 
seemed to be improving, yet the white cells had risen to 22,900. 
Operation was postponed owing to the lack of all unfavorable symp- 
toms except the blood count. Next day the bowels were moving 
well and the patient had no fever and no bad synptonis of any kind, 
but his leucocytes had risen to 35,300. On the following morning 
the surgeon was finally persuaded to operate and found a large 
amount of pus. Four times this series of events has fallen under 
my observation. 

A steadily increasing leucocytosis is always a bad sign and 
should never be disregarded even when (as in these cases) other 
bad symptoms are absent. It is of far more significance than a 
larger count which does not increase. 

6. The size of the leucocytosis is of comparatively little signifi- 
cance. A low count (8,000-11,000) means one of three things: 

(a) A mild case. 

(b) A very severe case. 

(c) An abscess thoroughly walled off. 

After the abscess has ceased to spread and has become well 
walled off, the leucocyte count remains stationary or decreases. If 
it bursts into the general peritoneal cavity the count may rise 
sharply or it may fall to normal or subnormal, its movement de- 
pending on the degree of resistance which the system offers. 

7. In the majority of cases the pus is neither completely walled 
off nor free in the belly, and such cases are accompanied by a mod- 
erate and fluctuating leucocytosis, which rises and falls according 
to a variety of conditions which cannot be accurately interpreted. 

It usually increases in the first three or four days of the illness, 
and then becomes stationary or declines if the case is taking a 
favorable course (i.e., if the pus is being absorbed or walled oif), 
while it continues to increase when the case is going on from bad to 
worse. 



250 SPECIAL PATHOLOGY OF THE BLOOD. 

Case 20 illustrates the course of the leucocytes in a favorable case 
not operated on; the leucocytes fell gradually but steadily from 
liour to hour so tliat in two days the couut came down from 20,100 
to 8,750, the tumor and tenderness simultaneously disappeared, and 
the patient was well in a few days more. Case .')8 dropx:)ed in eight 
liours from 16,000 to 8,000 and quickly recovered. In Case 19, 
the leucocytosis feJl in three days from .33,000 to 9,200, but rose 
again when the bowels were moved by enema, and took some days 
to reach normal again. Evidently the peristalsis injured the abscess 
wall so that the process began to spread again and liad t(j be walled 
oft' afresh. 

8. When a leucocytosis of 18,000-lC),(l()0 is nudntaincd for a 
number of days it usually means a large abscess i)retty well walled 
off. 

9. The majorit}^ of cases as seen at the Massachusetts General 
Hospital on the second, third, and fourth days of the illness showed 
leucocytosis of 15,000-24,000, thirt^'-three of the present series 
falling within these figures. Counts larger than this have always 
been proved to mean a large amount of pus, a general peritonitis, 
or a complication such as pylephlebitis or hepatic abscess. Of the 
cases below 15,000 (fifteen in all) twelve did not come to operation, 
or if operated showed no pus. This statement excludes the four 
cases of general purulent peritonitis without leucocytosis mentioned 
above. 

10. Case 18 illustrates several points. After the first operation 
the leucocyte count did not fall so rapidly as usual, and tlie cause 
of this soon turned out to be a pus pocket, after the evacuation of 
which the count fell in twenty-four hours from 47,700 to 16,700, 
only to rise again for another accumulation of the same kind. 

After this last (third) operation the case progressed slowly but 
favorably, and yet the leucocyte count remained more or less above 
normal for a month. The wound was healthy, freely discharging, 
and had healed satisfactorily at the time of the last count reported. 

Bloodgood ' has studied a considerable group of cases with mucli 
care and his results deserve our attention. He properly lays great 
stress upon the element of time in the interpretation of leucocyte 
counts. He divides his cases primarily into the acute and the 
chronic, and then makes a second set of distinctions among the acute 
cases, which will concern us later. 

^ Bloodgood : Prog. Medicine, December, 1901. 



APPENDICITIS. 251 

I. The 29 chronic cases in his series (all operated upon) include 
those admitted at the end of an attack, or between attacks, and 
found at operation to be unassociated with pus. Twenty-four of 
these had counts below 12,000, while the other live ranged between 
12,000 and 15,000. The latter were in cases admitted at the end of 
an attack and still presenting slight symptoms. 

II. («) Acute Diffuse Appendicitis without Pu^ ("catarrhal"). 
In 22 cases (all operated on) there was one count of 22,000 

(twenty hours from the lirst symptom), rapidly falling to 11,000 
within twenty-four hours, and two counts of 17,000, falling within 
forty-eight hours to normal. The other cases showed lower counts. 

(h) Gaiuji'ciious Appendicitis (10 cases, no pus). 

In cases seen early in the attack a rapid rise of the leucocyte 
count can be observed to 20,000 or more. 

(r') Acute Appendicitis with Pus Distending the Organ. 

The counts in four cases were practically like those in gangre- 
nous appendicitis. 

{<}) Apj>endicitis 'witJi Abscess. 

In 14 cases of Bloodgood's series (26 per cent) the leucocyte 
count was normal (6,000-12,000). In 11 of the 14, the history and 
tlie other symptoms pointed to a chronic, well-encapsulated abscess. 
In 3 there were acute local symptoms, and 2 of these were extremely 
ill — presumably unable to react. 

In 9 cases — subacute or chronic with palpable tumor — the 
counts ranged between 12,000 and 15,000. 

In 33 cases (63 per cent) the leucocytes numbered 15,000 to 
60,000— the great majority over 18,000. All were above this figure 
if seen within the first forty-eight hours. 

(e) Appendicitis with General Peritonitis. 

The counts may be high or low. Four of Bloodgood's cases 
sliowed respectively 11,000, 11,000, 13,000, and 14,000 (all fatal). 
These were all cases of at least three days' duration, and as in cases 
observed within tlie first forty-eight hours, he has often (as I have) 
found higli counts, he concludes that "in the early hours of peritoni- 
tis there is a rapid rise in the leucocytes, which, however, soon falls." 

In view of all these facts, Bloodgood considers that: " Withii. 
the first forty-eight hours a leucocytosis of 18,000 should be con- 
sidered an indication for operation," especially if we have recorded 
a rising leucocyte count. With a count below 18,000 and falfoHj 
^'he patient is recovering from the attack. 



252 SPECIAL PATHOLOGY OF THE BLOOD. 

Between the third and .seventh day a leucocytosis of 18,000 or 
more is usually an indication for immediate operation, but in some 
cases the local signs may incline u.s to postpone operation. 

The above agrees essentially with the opinion of Longridge/ of 
Klihn,^ of Coste,^of Locke, ^ and of Joy and Wriglit' 

The latter observers lay especial emphasis on the good ijvoyiiosttc 
significance of a decreasing leucocytosis. In such cases, unless the 
falling count is accompanied by unmistakable signs of a generally 
bad condition (which is rarely tlie case), operation may be post- 
poned, while a higlt stationarg or increasing count indicates a pro- 
gressively serious case which demands immediate intervention. This 
is entirely in agreement witli my own experience. 

Curschmann,'"' Kuttner,' Diitzmann," Blassberg,' and Weiss '" ex- 
press similar views, Kuttner especially insisting upon the need of 
making at least two counts a day and controlling them with the iodiDe 
reaction (see below). If carried out with these ^precautions Kuttner 
considers the count of leucocytes a most valuable aid in distinguishiug 
post-operative aseptic fever from pus-pocketiiig. Curschmann \m'- 
lieves that a single count of 25,000 or more should make us veiy 
suspicious of the presence of pus, though, like all other recent ob- 
servers, he deprecates reliance on single isolated counts and urges 
leucocyte charts. Blassberg believes that leucocytosis is less marked 
in peripheral than in abdominal suppurations. 

From these quotations it appears that our German colleagues are 
at last waking up to the importance of blood counts in suspected 
deep abscess, and are going through for the first time experiences 
familiar to American physicians since 1893. Indeed, there are 
indications that some German surgeons are falling into the error so 
common here ten years ago — the error of supposing that leucocytosis 
always means pus. Against this mistake Grawitz warns his coun- 
-trymen in the latest edition of his excellent text-book. Deaver '^ in 
this country has uttered similar and on the whole very valuable 

^ Longridge: Brit. Med. Journal, November 8th, 1902. 

2 Kiihn: Munch, med. Woch., December 9th and 16th, 1902. 

3 Coste; Ibidem, December 9th, 1902. "^ Locke (see p. 255'. 
5 Joy and Wright: Medical News, April 5th, 1902. 

^ Curschmann: 31st German Surgical Congress, April, 1902. 

'Kuttner: Ibidem. "Diitzmann: Ibidem. 

» Blassberg: Wien. klin. Woch., November 20th, 1902 
^•^ Weiss: Ibidem, January 15th, 1903. 
^' Deaver: Transactions of Am. Surg. Assn., 1901, p. 115. 



APPENDICITIS. "Abo 

warnings against the "tendency to replace the l)edside by the labo- 
ratory as the point from whicli to make the diagnosis." When such 
a choice must he DKide sensible men will generally agree with Deaver 
that the bedside is the point of vantage. But as Da Costa and 
others have pointed out, we need rarely make this most unfortunate 
division between the different methods of physical diagnosis. The 
microscope should be a " laboratory " instrument no more than the 
thermometer. 

The matter cannot be l)etter summed up, I think, than in the 
words of Da Costa : '" The surgeon who attempts to use the blood 
count in appendicitis as a definite pathognomonic sign will soon 
run afoul of diagnostic disasters, but he who regards it only as a 
symptom invariably to be correlated with equally, if not more 
important, clinical manifestations, cannot fail to find this method of 
inquiry of signal value in routine clinical surgery." 

I am likewise in hearty agreement with another statement of Da 
Costa's: "The behavior of the leucocytes throws a much clearer 
light upon the progress of the disease, both in operative and non- 
operative cases, than it does upon the initial diagnosis, which should 
be determined chiefly by other clinicial methods." But to inter- 
pret aright the variations of the leucocytes after operation, we need 
to be familiar with those changes in the blood due to the operation 
itself, and to the anaesthetic which made it possible. Accordingly, 
I shall next discuss : 

I. The Effects of General Narcosis on the Blood; and 

II. Post-Operative Changes in the Blood. 

I. The Blood Changes Produced by General Narcosis. 

The earlier literature is well summarized by Da Costa and 
Kalteyer.^ Their own studies in fifty cases lead them to the fol- 
lowing conclusions : 

1. Following anaesthesia there is generally a polycythsemia, rarely 
an oligocythsemia. The polycythgemia is most marked immediately 
after the termination of the anaesthetic stage, probably due to a con- 
centration of the blood from previous purgation and recent vomiting. 

2. Haemoglobin is invariably reduced absolutely, although the 
amount of ether used and the duration of anaesthesia probably influ- 
ence the blood change to a moderate extent. 

^ Da Costa and Kalteyer: Aimals of Surgery, September, 1901. 



2,34 SPECIAL PATHOLOGY OF THE BLOOD. 

3. The amount of blood lost by operative hemorrhage seems to 
have little effect upon these changes. 

4. Owing to the haemolysis following anaesthesia, the writers l>e- 
lieve that no oj)eration can be safely done when the haemoglobin is 
below fifty per cent. 

Fish ^ has previously reached similar conclusions, while Mikulicz 
puts the percentage at 30. Bloodgood* details a case in whicli tli»^ 
red cells fell from 3,076,000 before operation to 2,000,000 twenty- 
four hours later, while the haemoglobin fell from 54 per cent to 30 
per cent, despite the fact that there was ])ractically no loss of lOood 
at the operation. 

Despite all this important evidence, which goes to show the nar- 
cosis may be dangerous in anaemic patients, we must not forget that 
it may be even more dangerous to postpone operation. Hence it 
may be the surgeon's dut^^ to operate under local anaesthesia or to 
face the danger of general narcosis as the lesser of two evils. 

The Lfucocijte Count Durliuj <iinl Aftrr Xarcosis. 

The studies of Da Costa and Kalteyer {lot-, rit.) and of Cabot, 
Blake, and Hubbard ' have proved that the effect of etherization on 
the leucocytes is practically nil. Tliey were unable to confirm the 
results of Chadburne.^ 

II. Post-Operative Changes ix the Blood. 

In the studies of Cabot, Blake, and Hubbard counts were made 
after full anaesthesia and again at the close of the operation in 
36 cases. In 11 of these (30 per cent) there was a distinct leuco- 
cytosis varying from 19,000 to 27,000, which appeared to be due 
rather to the nature and extent of the operation than to the anaes- 
thetic. King's ^ studies indicate that an increase of from 5,000 to 
10,000 over the count before operation is a very common phenome- 
non within the first fortj'-eight hours following operation and is of 
no significance j>;'or/W^^ it is not sustained. The maximum is 
reached within twelve hours after operation. 

White ® found an average of nearly 21.000 per cubic jnillimetre 

^ Fish: Anuals of Surg., 1899, vol. xxx., p. 79. 

2 Bloodgood: Prog. Med.. December, 1900. 

3 Cabot, Blake, and Hubbard: Annals of Surg., 1901, p. 361. 
^Chadburne: Phil. Med. Jour., February 18th, 1899. 

^King: American Jour. ]\[ed. Sciences. 190"2, vol. cxxiv., p. 450. 
«AYhite: Univ. Med. 3Iao-., Mav 13tli. 1001. 



APPENDICITIS. 



255 



after laparotomy with an absolute (and usually relative) increase of 
polynuclear cells and absence of eosinopMles. 

The degree of leucocytosis seemed to depend upon the severity 
of the operation. The highest counts were found about five hours 
after operation. From this time the number of leucocytes gradu- 
ally diminished, reaching normal, on the average, in about five days. 

If complications occur, the leucocyte count remains elevated, or 
is slower in falling. Frazier and Holloway ^ who studied forty 
cases and did not confine themselves to laparotomies, found that 
three and one-half days was the average duration of post-operative 
leucocytosis in uncomplicated cases. White found that in cases 
sewed up tight the leucocytes returned to normal more rapidly than 
in those drained. In the latter cases the slight infection along the 
drainage tube probably accounted for the fact that the post-oper- 
ative leucocytosis usually lasted more than five days. My own 
observations tally very closely with the above and I shall not repeat 
them in detail. 

lodophilia. 

The studies of E. A. Locke " in sixty-one cases of appendicitis are 
so interesting that I have inserted his tables entire. The leucocyte 
count and the iodine reaction were taken immediately before oper- 
ation and their indications carefully compared with the pathologi- 
cal conditions found at operation. 

Table XXII. — Intep.val Appendicitis. 



Intracel- 
lular. 



Extracellular. 



Whites. 



Remarks. 



Absent. 

Aibsent. 

Absent. 
Absent. 
Absent. 

Absent. 

Absent. 
Absent. 



Slightly increased. 
Slightly increased. 



Normal 

Normal 

Slightly increased. 

Slightly increased. 

Slightly increased. 
Xormal . 



9,000 Temp. 98.8 . X'o inflammation. 

Adhesions. 
11,000 ] Numerous adhesions. No inflam- 

I mation. 
12,000 i Few adhesions. No inflammation. 
7,000 ; Temp. 98.8°. Many adhesions. 
8,000 I Temp. 99^ Many adhesions. No 

1 inflammation. 
10,500 I Old adhesions and moderate in- 

j flammation, 
12,000 ' Appendix thickened and adherent. 
12,000 I Chronic inflammation. 



' Frazier and Holloway: Univ. of Penn. Med. Bull., December 1901. 
^ Locke: Journal of Medical Research, .January, 1902 (literature here ab- 
stracted), and Boston Medical and Suigical .Touni.il, September 11th, 1902. 



25(; 



SPECIAL PATHOLOGY OF THE BLOOI). 



Tabj.e XXIII. — AcrTK Appendicitis without General Peiutomtis ok 

Local ABSCEf^s. 



^ '\ Intracellular. 


Extracel- 
lular. 


Whites. 


Duration. ' Remarks. 


1 

0, 


Faint 


Increased. 
Increased. 

Xorraal.. . 

Xormal... 

Increased. 


22,000 
24.000 

14,000 

20,000 

15,000 


3 days. | Temp. 101.1 . 

'Temp. 101.6. Appendix 

much inflamed. 

Small, red appendix, with 

1 adhesions. 
Appendix moderately in- 
flamed. 
8 hours. Temp. 100\ Appendix 
' considerably inflamed. 


Faint 


?, 


Faint 


4 


Faint 


5 


Slight coloration 



Tahi.e XXIY. — Appendicitis with Local Abscess, bit withoct Gen- 
eral Peritonitis. 



z 


Intracellular. 


Extracel- 
lular. 


Whites. 


Duration. 


Remark.-*. 


1 


Faint 


Increased. 
Xormal . . 


14.000 
17,000 


4 days. 


Few drops pus walled off. 
Gangrenous a ji p e n d i x. 


2 


Fair 












Small abscess. 


8 


Fair 


Increased. 


15,000 




Temp. 101 . Big abscess. 


4 


Fair 


Xormal . . 


27,000 




Temp. 1(11.6 . Few drops 


5 


Fair 


Increased. 






pus. 
Perforated appendix. 










Small amount of pus. 


0. Good 


Increased. 


20,000 


4 da vs. 


Temp. 104'. Appendix 












gangrenous. Small ab- 












scess. 


r- 


Good 


Xormal . . 
Increased. 

Increased. 


14,000 
18,000 





About one ounce pus. 
Small abscess well walled 


8 


Good 


9 


Good 


off. 
Gangrenous a p p e n d i x . 
Small abscess. 










10 


Good 


Increased. 


24,000 


4 days. 


Temp. 102 \ Pus burrow- 
ing beneath the mesentery. 


11 


Marked 


Increased. 


7,400 




Enormous abscess. Death 
in few hours. 


12 


Marked 


Increased. 


20,000 




Perforated, local peritonitis. 


18 


Marked 


Xormal . . 


16,000 


6 days. 


Small pocket of pus. 
Temp. 102. 9 \ 


14 


Marked 


Increased. 


10,000 


24 hours 


Temp. 105". Small abscess. 


15 


Marked 


Increased. 


21.000 


8 weeks 


Temp. 101 \ Laree abscess. 


16 


Marked 


Increased. 


36,000 




Small amount of pus not 
walled off. 


IT 


Marked 


Xormal . . 


80,000 




Gangrenous appendix. 
Little free pus. 


18 


Marked 


Xormal . . 


25,000 


3 weeks 


Small abscess walled off. 


19 


Marked 


Increased. 


8,000 


3 days. 


Temp. 102.5'. Pus not 
walled off. 


tiO 


Marked 


Increased. 


20,000 


6 davs. 

* 


Temp. 99 \ Pus partiallv 












walled off. 



APPENDICITIS. 



257 



Table XXV. — Appendicitis with General Peritonitis. 



1 


Intracellular. 


Extracellular. 


Whites. 


Remarks. 


1 

9, 


Very marked. 

Very marked. 

Marked 

Marked ..... 
Marked 

Marked 

Marked 

Marked 

Marked 

Marked 

Marked 

Moderate 

Good 

Good 


Much in, 
creased. 


40,000 

24,000 

20,000 

28,000 
27,000 

13,400 

14,000 
16,000 

4,800 
8,000 

13,000 

j 19,000 

} 15,000 

52,000 

33,000 

25,000 
18,000 
12,000 

17,000 

30,000 

12,000 


Much free pus. 

Perforated appendix and mild 
general peritonitis. 

Temp. 101°. Streptococcus in- 
fection. 

Considerable free pus. 

Perforated appendix. Much free 
pus. 

Perforated appendix. Little free 
pus. 

Temp. 105.5°. Traumatic origin. 

General infection of peritoneum. 
No pus. 

Abdomen full of pus. 

Abdomen full of pus. 

Abdomen full of pus. 

Appendix abscess. Not walled 
off. 

Perforated appendix. Earl}' 
peritonitis. 

No free pus. 

Temp. 103.6°. Extensive inflam- 
mation. 

Temp. 99.7° No pus. 

Temp. 103.° 

Typhoid perforation. No pus. 
Six hours' duration. 

Temp. 102.8°. Free fluid. Cul- 


3 

4 
5 

6 

7 
8 

9 

10 

11 

12 

13 

14 


Much i n - 
creased. 

Normal 

Increased . . 

Increased . . 

Increased . . 
Normal . . . 

Increased . . 

Greatly in- 
creased. 

Greatly in- 
creased. 

Normal .... 

Normal 

Increased . . 
Increased . . 

Increased . . 
Normal 


15 


Good 


16 

17 


Good 

Good 


18 


Good 


19 


Fair 


Increased . . 
Increased . . 


20 
?-1 


Fair 

Faint 


ture sterile. 

Bullet wound of abdomen. At 
autopsy some general inflam- 
mation, but no pus. 

Temp. 98°, nine hours after per- 
foration of gastric ulcer. Mild 
inflammation. No pus. 









In general tlie intensity of the intracellular reaction appears to 
indicate the severity and duration of the process on the appendix 
and the amount of septic absorption from the focus. W^hen the 
amount of pus is small and thoroughly encapsuled (as in Table 
XXIV., Case I.) the reaction may be faint. But the point of great- 
est interest is the occurrence of a marked iodine reaction without 
leiicocytosis in some of the most virulent cases. (See Table XXIV., 
cases 11, 14, and 19, and Table XXV., cases 9 and 10.) Here the 
indications of the iodine reaction act as a most valuable control and 
correction upon those of the leucocyte count. 
17 



258 SPECIAL PATHOLOGY OF THE BLOOD. 

With the free drainage of pus, the brown granulation in the 
leucocytes rapidly diminishes, and is usually gone within forty- 
eight hours. Persistence of the reaction indicates incomplete drain- 
age. The iodme reaction, like the leucocyte reaction, means usu- 
ally septicaemia, but not always pus. It is present in cases of 
grave anaemia, and in a variety of toxic and infectious conditions 
(malaria, uraemia, grave anaemia, carbon monoxide poisoning, etc.), 
some of which produce leucocytosis, while others do not. Its 
value consists in the fact that it adds another to our list of clinical 
indications of the presence of toxaemia — such indications as pyrexia, 
tachycardia, albumosuria, and leucocytosis. ISTone of these is pres- 
ent in every case and any of them may be present when toxaemia is 
absent. Hence the addition of an independent indicator like iodo- 
philia to our list strengthens our diagnostic resources consideral)ly. 

Occasionally we have infectious or suppurative processes with- 
out pyrexia or tachycardia. Karely we have infectious or suppu- 
rative processes without pyrexia, tachycardia, or leucoc^^tosis. 
Never (so far) have infectious or suppurative processes occurred 
without pyrexia, tachycardia, leucocytosis, or iodojjhilia. 

The diagnostic value of a negative reaction is therefore great, 
for as Locke says : 

" Septic conditions of all kinds, including septicaemia, abscesses 
and local sepsis, except in the earliest stages, appendicitis accom- 
panied by abscess formation or peritonitis, general peritonitis, em- 
pyema, pneumonia, pyonephrosis, salpingitis with severe inflamma- 
tion or abscess formation, tonsillitis, gonorrheal arthritis and hernia, 
or acute intestinal obstruction where the bowel has become gangre- 
nous, have invariably given a positive iodophilia, and by its absence 
all these cases can be ruled out in diagnosis. In other words, no 
septic condition of any severity can be present without a positive 
reaction." 

On the other hand, he has failed to get a positive reaction in 
extra-uterine pregnancy, in dry and serous pleurisy (sixteen cases), 
in uncomplicated tuberculosis, in bronchitis, and in articular rheu- 
matism (twelve cases). 

The further indications of the iodine reaction will be considered 
in the sections on the different diseases investigated. 



APPENDICITIS. 259 



I)}fferential Diagnosis. 

1. The presence of a inaiked leucocytosis excludes simple colic 
with or without constipation. 

2. Post-operative malaria/, Avhich may break out in patients who 
are aware of no previous attacks or who have had none for months, 
produces fever and chill like those due to pus-pocketing perito- 
nitiSj pylephlebitis, or other post-operative complications. The 
discovery of the malarial parasite and the absence of any marked 
leucocytosis serve to identify malaria, while in the other affections 
leucocytosis is high and persistent. 

3. Treves ^ has reported several cases in which it was hard to 
decide whether the diagnosis was typhoid or appendicitis. A blood 
examination would probably have decided the matter, as it has in 
three cases in the writer's experience. Most cases of appendicitis 
of any severity show leucocytosis; typhoid almost never does if un- 
complicated. Curtis ^ reports a case of typhoid with a tumor and 
tenderness in the right iliac region which closely simulated appen- 
dicitis, but turned out to be a floating kidney. The blood count 
would have decided the matter. 

4. Between appendicitis and pus tube the blood gives no help, as 
both affect it alike. 

5. Ovarian or pelvic neuralgia (uncomplicated) never causes 
leucocytosis and may be excluded *by its presence. The same is 
true of floating kidney, which has been sometimes confounded with 
appendicitis. 

6. Gall-stone colic, and renal colic if uncomplicated by inflam- 
matory disturbance, cause no leucocytosis, and can therefore be 
distinguished from appendicitis in most cases. If cholangitis, 
cholecystitis, pyelitis, or severe cystitis complicate the colic, the 
examination of the blood will be no help to us. 

7. Impaction offceces in the caecum will not cause any leucocy- 
tosis and may be excluded when such is present. The count may 
be of use, it seems to me, in deciding us whether an enema ought 
to be given. It is sometimes desirable to give an enema in cases 
simulating appendicitis, to help clear up the diagnosis; but some 
physicians are afraid to do so for fear of causing a walled-off abscess 

MVIedico-Chirurgical Transactions, 1888, Ixxi., p, 165. 
-Twentieth Century Practice of Medicine, vol. viii., p. 461. 



260 



SPECIAL PATH()LO(iV OF THE BLOOD. 



to break into the general peritoneal cavity. In such cases, if no 
leucocytosis were i:>i^esentj we might go ahead with a clearer con- 
science. 

Mr. B entered the Massachusetts General Hospital, Septem- 
ber 20th, 1893, with a diagnosis of appendicitis. For twenty days 
he had been having pain and tenderness in the region of the appen- 
dix, pain being controlled by morphine. The bowels had been 
loose, he said. There were dulness, tenderness, and a distinct 
tumor in the region of the appendix, with slight pyrexia. The 
blood count showed only 8,000 leucocytes. He was given a com- 
pound cathartic pill, had a large movement of the bowels, and all 
symptoms and signs disa])pearecl. 

8. Extra-att'i-ini' prtujitamyj and pelvic haematocele may cause 
leucocytosis like appendicitis, but do not increase fibrin unless peri- 
tonitis is present, and are ]ikely to slioiv a marked diminution in red 
corpuscles if the hemorrhage is severe. The red cells are normal in 
appendicitis except in chronic cases with abscess. 

9. Floating kidney has been already mentioned in Curtis" case, 
in which in combination with typhoid it closely resembled appendi- 
citis. Even without the presence of typhoid, the same difficulty of 
diagnosis may arise between appendix and floating kidney. Tin- 
presence of leucocytosis could ]iot be accounted for by the latter. 

One of the next most common forms of abscess seen in medical 
wards is pyosalpinx, which I shall call by the English name of 
"pus tube." As this produces the same effect on the blood as ap- 
pendicitis or any other abscess I shall not repeat the general con- 
siderations just discussed. 

PUS TUBE, PELVIC ABSCESS, AND PELVIC PERITONITIS. 

Almost all that has been said of appendicitis applies equally 

well to these conditions. 



Table XXVI. 



-Pts Tube and Pelvic Abscess. 



i 


< 

42 
36 




Red cells. 




III 


Remarks. 


1 


F. 
F. 




46,000 
44,000 
45,000 
43,000 
31,000 
45,900 


80 


January 2d. General peritonitis : double pus tube; Death. 

January otb. 

January Ttb. 

Double pus tube ; too weak to operate. December 1.5th. 


«3 












Dereiriher 29th : abscess burst per vaginam. 



PUS TUBE, PELVIS ABSCESS, ETC. 



261 



Table XXVI., A. — Pus Tube and Pelvic Abscess — Continued. 











S» 


III 

m 




6 
2 




1 


Red cells. 


m 


Remarks. 










20,200 
15,200 
12,200 




January 4th, abscess opened in groin. 
January 8tli. 
January llth. 


H 




F. 


5,400,000 


34,200 




Pelvic abscess. 


4 


88 


F. 




34,200 




Pus tube. June ISth. 










34,600 




June 19th, 










35,000 




June 20th. 










40,000 




June 27th, fever and vomiting lust before catainenia. 










17,300 




July 1st, temperature normal. 










11,.500 




July 8th, mass decreasing. 










12,000 




July 14th, slight thickening still. 





10 


F. 




33,500 


65 


Acute localized peritonitis. 


6 


84 


F. 


4,202,000 


35,.500 


60 


Pus tube; septic arthritis ; .laundice. 


7 




F. 


4,880,000 


30,000 




Pus tube. 


H 


«8 


Y. 




29,200 




Double pus tube. 


9 


29 


F. 


4,-544,000 


28,800 




General purulent peritonitis. 


III 


r'O 


K 




27,800 




Pus tubes. 


11 


26 


F. 


3,8tX),000 


27,000 
25,000 


65 


Double pus tube. November 17th. 
November 19th, operated. 


VZ 


25 


F. 




27,000 


65 


August 22d, pelvic abscess. 










20,000 




August 24tb. 


18 


48 


F. 


5,210,000 


26,600 




Pus tubes. 


14 


25 


F, 




25,400 


85 


Pelvic abscess. 


15 


28 


F. 


5,120,000 


24,400 




Pus tube. 


m 




F. 




24,4(X) 




Pus tube four weeks' duration. 


17 


24 


F. 


5,376,000 


24,000 




Pus tube. 


IK 


•>A 


F. 




23,600 


85 


November 11th. Pus tube. 










12,01)0 




November 13th. 


19 




F. 


3,760,000 


23,000 




Pelvic abscess (fetid pus). 


'r^l 


27 


F. 




22,60(1 
17,500 


85 








February 10th. 










10,000 




February 11th. 










12.900 




February 1.5th. 










16.900 




February 17th. 










13,200 




February 19th. 










18,000 




February 21st. 










19.400 




February 23d. 










20,400 




February 24th. 


ai 


45 


V\ 




22,000 




Pus tube. 


2Ji 




F. 


5,200,000 


22,000 




Pus tube. 


28 




F. 


5,200,000 


22,000 




Pus tube ; operation ; pus found. 


^ 


85 


F. 


3,704,000 


21,100 


65 


Pus tube operated. 


:i5 


19 


F. 




20,200 




May 1st. 










23,800 




May 11th, mass the same ; pus tube. 


»'6 


26 


F. 


5,031,000 


20,000 




Pus tube. 






F. 


4,400,000 


19,800 




Pus tube. 


;-^K 


'M 


V 




19,000 




Pus tube. Temperature 99°. April 26th. 










21,100 




No fever. May 2d. 










16,000 




May 4th. 










18,600 




May 9th. 










19,600 




No fever. 










21.600 
18,200 
16,300 





May 18th, flovsr of pus from os started by manipulation. 












Outdoors. 


^ 


54 


F. 


3,940,000 


19,000 


60 


Pus tube and ovaritis; operation ; pelvis full of foul pus; 
recovery, after hysterectomy. 


30 


25 


F. 


8,860,000 


18,800 




Pus tubes. 


81 


? 


F. 


4,592,000 


18.800 




Pus tube. 


8V 


*/1 


F 




18,600 


68 


July 81st, pelvic abscess. 
August 1st. 










16,000 












13,000 




August 6th. 










18,000 




August 11th. 


88 


18 


F. 


3,840,000 


18,500 


55 


Pus tube ; three hours after food. 


84 


82 


F. 


5,776,000 


18,000 




Pus tubes. 


85 


28 


F. 


5,000,000 


18,000 




Pus tube. 


86 


80 


F. 


3,410,000 


18,000 




Pus tube, etc. 


87 


21 


F. 


5,088,000 
5,184,000 


16,400 
18,000 




Pus tube, syphilis. October 7th. 
October 12th. 


8H 


22 


F. 


4,300,000 


16,000 


80 


Pus ear. 


89 




F. 


3,800,000 


16,000 




Puis tube, 



262 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXVII., A.— Pus Tube and Pelvic Abscess {(Jontinned). 





i 


t«3 


'^ 


< 


CO 


40 


35 


F. 


41 


36 


F. 


4:> 


21 


F. 


43 


50 


F. 


44 


19 


F. 


45 


36 


F. 


40 


20 


F. 


47 


26 


F. 


4H 


21 


F. 


4!) 


38 


F. 


AO 


25 


F. 


Al 


22 


F. 


52 




F. 


58 


35 


F. 


54 


21 


F. 


55 


19 


F. 


5H 


36 


F. 


iTl 




F. 


58 


18 


F. 


59 


33 


F. 


60 


18 


F. 


61 


47 


F. 


62 


21 


F. 


m 


44 


F. 


64 




F. 


65 


38 


F. 


66 


24 


F. 


67 19 

i 


^• 


1 
68il9 


F. 


69124 


F. 


70 


19 


F. 


71 


23 


F. 


72 


21 


F. 


7;i 


21 


F. 


74 


29 


F. 


75 


23 


F. 


76 




F. 





a.' . 






Red cells. 


>^^ 




15,600 




18,200 


4.656,0(HJ 


15,600 




15,-500 




4,500 





15,400 




21,600 




1.5,300 
14,975 


3,696,(K)0 




12,600 


4,310,(MX) 


14,800 




14,700 
14,700 
11,2a) 








9,000 




9,000 


3,008.1K)0 


13,853 




13,-500 
]3,(X)0 






10,(X)0 




26,800 




1.5,000 




11,000 




6,000 




14,800 




15,000 


4,700,(K)0 


12,500 




12,200 
12,200 
12,300 






3,910,000 


12,0tK» 




12,000 


4,756,000 


11,850 




13,750 




11.300 
11,000 


4,240,000 




10,800 
10,600 






11,000 




11,500 


8,800,000 


10,400 




10,200 




14,130 


7,000,000 


10,000 


4,125,000 


10,000 




17,000 




13,400 




9,900 
9,800 






20,900 




14,000 




9,200 




9,000 




9,200 




8,900 




8,200 




8,200 J 




8,200 1 




7,900 1 




7,.500 




12,200 




14.300 




9,400 




10,200 1 


472,000 


7,500 1 


5,840,000 


7.200 



70 



60 



64 



85 



operate" I. 
chlornsis. 



Pus tube. May Hth. 

May 18th. transferred. 

Pus tube; birge amount of pus found. 

December 31st, salpirifnti>. 

January 2d. 

May 6tli. i»us tul)i-. 

I May 9th. 

'Pelvic i)eritonitis. 

48 iPus tube. .lulv 2Nt. ijiiils and delirium. 

July 2kl. 

July 25th 

Pus tube 

Pus tube. 

January 17tli. pu< tube. 

JaiHiarv istli. 
.Jaiuiarv liitli. 

January 2iitii. 

Pus tube. 

Pus tube. 

Jan. 1st, pus tube. 

Jan. 2d. 

Jan. 8th. 

Jan. 10th. 

Jan. 14th. 

Jan. 19th. 

Jan. .•i5th. 

Jan. 30th. 

Pus tube (double); « 

|Pus tube; slifrht. 

Pus tube, .lime 2d 

June 10th. 

Pus tube. 

Pus tube. 

Pus tube 



iperated. 



Jaiuiary 5tli and Oih. 

Pus tube. 

Pus tube. Not operated; very slljrht. 

Pus tube. 

Chronic salpingitis. June 2Isl. 

June 25tli. better. 

June 29th. 

Pelvic peritonitis. 

June od, pus tube. 

June 24th. 

Pelvic abscess (?) . 

Pelvic abscess. August 2Sth. 

September 3d. temperature up. 

September 6th. normal temperature. 

Pus tube. 

November 16th, Pus tube. 

November 27th. 

November 30th. 

Pus tube. 

Salpingitis. 9 a.m. ; Temp. 99.4°. 

4:15 P.M.: five days in hospital. 

Pus tube, 

Pus tube. 

Pus tube. 

Pus tube. 

August 4th. 

August 5th. 

August 6th. 

August 7th. 

August 9th. 

August 11th. 

Pus tubes (small, size of flnger). 

Pus tube. 



OTITIS MEDIA. 263 

Pus Tube, Pelvic Abscess, and Pelvic Peritonitis. 

White Cells. Cases. 

Between 7,000 and 10,000 11 

10,000 " 12,000 9 

12,000 " 14,000 8 

14,000 '• 16,000 9 

16,000 '■ 18,000 3 

18,000 " 20.000 10 

20,000 " 22,000 3 

22,000 " 24,000 6 

24,000 " 26,000 4 

26.000 " 28.000 4 

28,000 •' 34,000 5 

34,000 or more 4 

76 
From these data, together with two hundred and nineteen other 
counts not here recorded, I conclude that increasing counts of leu- 
cocytes usually point to the need of an operation; stationary leuco- 
cytosis to a well walJed-off abscess. The size of the count is a 
rough measure of the size of the abscess, and patients without leuco- 
cytosis rarely need operation and usually recover under palliative 
treatment, as also do many ivith leucocytosis. 

Differential Diay7iosis. 
Pelvic pain and soreness may be as great in various non-suppura- 
tive conditions (ovarian neuralgia, etc.) as when abscess is present; 
but the leucocyte count is raised in none of the pelvic disorders of 
women except in abscess, septiceemia (puerperal, after abortion, etc.), 
and hemorrhage (menorrhagia, metrorrhagia, ruptured tubal preg- 
nancy). Endometritis and cystitis usually cause no leucocytosis. 
The application of these rules will not infrequently help in the 
diagnosis of pelvic disease and in deciding how much importance 
to attach to the complaints of pain, tenderness, etc., in a doubtful 
case. The absence of leucocytosis makes us rightly confident that 
no abscess of any considerable size exists. 

OTITIS MEDIA. 

Most cases, if purulent, show leucocytosis both before and after 
paracentesis. If serous (see Table XXVIII., cases 9, 17, 18, 21, 
23) the count is usually lower, and we can predict with moderate 
certainty whether serum or pus will be found on puncturing the 
drum. When the mastoid is involved the count runs higher. If 



264 



SPECIAL PATHOLOGY OF THE BL(JOD. 



the case drags on, the lisemoglobin may get low. otherwise the red 
cells are not affected. 

Table XXVIIL— Otitis Media. 











White 


Per cent 




6 


Age. 


>< 


Red cells. 


cells. 


haemo- 
globin. 


Remarks. 


1 


6 


F. 




36.700 
27,300 
34,400 
27,000 
21.000 


.. 


Nephritis acuta. April 30th. 

May 7th. 

May 14th, otitis only. 

May 22d. 

May 28th. slight discharge still. 


3 


15 






25,000 
12.000 
34,000 
24.000 
8,000 


90 

■ ■ 


January 22d, 
" ^ 27th. 
" 31st. 

February 2d. 
•' ' 4th. 


3 


2 


M. 




•23.U00 


55 




4 


19 






21,900 
13,200 
10,800 


•• 


Ninth, T. 103.6\ 
Eleventh, T. lOr. 
Fourteenth, T. 99\ 


5 


6 


M. 





18,600 


20 




6 


20 






17,000 
21.900 


■■ 


AVith jugular thrombosis. 
Third day. 


7 


25 


. 




15.000 


90 




8 


45 


M. 




14,500 




With cerebral abscess. 


9 


Adult. 


M. 


ii 786, boo 


16.800 




Serous. 


10 


47 


F. 


4,168,000 


16,600 


65 


Double purulent ; vent not free ; 
mastoid sore. 


11 


19 


F. 


5,120,000 


16,480 

8.800 


88 
49 


April 28th. 
May 5th, well. 


12 


27 






15.800 






13 


Adult. 


F. 


5,'942,b00 


15,200 




Pus. 


14 


u 


F. 


4,472,000 


14,750 


60 


December 7th, hysteria. 








5,416,000 


9.750 


46 


December 25th (during dyspnceic 
and cyanotic attack). 


15 


24 




........ 


14,200 


72 




16 


9 






13.900 






17 


32 






12.000 




Serous. 


18 


24 




4,"472,b00 


11.200 


20 


Serous. 


19 


22 






11.000 






201 


24 






10,400 


85 


Catarrhal. 
Serous. 


21 


27 


F. 


4*850,000 


8,500 


69 


22 


7 


F. 


4,416,000 


6.400 




Catarrhal. 


23 


Adult. 


F. 


4,100,000 


4,000 




Serous. 


24 


4 


M. 




j\Iaiked 

leuco- 

cvtosis. 




Purulent ; chronic right, acute 
left. Diff. 116 cells ; polymor- 
phonuclear cells, 57^ ; lympho- 
cytes, 31 ; eosinophiles, 3. 



In some cases the blood alone enables us to distinguish otitis 
and its effects from typhoid. In a case recently examined which 
several excellent clinicians pronounced typhoid, though there was a 
marked leucocytosis and no serum reaction, the autopsy showed pus 
in the jugular and lateral sinus but no typhoid. 



OSTEOMYELITES. 



265 



OSTEOMYELITIS. 

In five cases in which uo external opening was present, the pa- 
tient complaining only of pain in the bone, the counts of leucocytes 
were 29,600, 25,600, 24,310, 23,400 and 18,000 ; in each the pre- 
diction that pus would be found was verified at operation. Three 
differential counts in chronic cases with sinuses showed nothing re- 
markable, no increase of eosinophiles and no myelocytes. 

The diagnostic value of the blood in osteomyelitis seems to me 
considerable, inasmuch as it is difiicult by the symptoms alone to 
feel sure enough of the existence of pus to be willing to operate. 
•''Rheumatic pains," "growing pains," and neuralgia can be ex- 
cluded by the presence of leucocytosis. 

Other Abscesses. 

(1) Felon. — It is striking to see how small a collection of pus 
can raise the leucocyte count. Patients with felons containing less 
than one-half drachm of pus may have a leucocytosis of 15,000 to 
22,000. I have counted the blood in three such cases. The ele- 
ment of septicsemia must be considerable. It seems to make no 
difference whether or not the pus is under great tension. The leu- 
cocyte count does not fall sharply after the felon is opened, but 
gradually diminishes during the next seven to ten days. Even a 

(2) Gum boil raised the white cells to 27,000 in one case. An 

(3) Abscess of the vulva showed 23,500 leucocytes per cubic mil- 
limetre, and an 

(4) Abscess of the vagina 12,800. Other varieties are: 

(5) Parotid abscess^ 45,500 leucocytes per cubic millimetre. 

(6) Subpectoral abscess, 16,000 leucocytes per cubic millimetre. 

(7) Abscess of the neck, 22,200 leucocytes per cubic millimetre 
Carbuncle, 41,000 leucocytes per cubic millimetre. 

(8) Peritonsillak Abscess — Six Cases. 



Case. 


Age. 


White cells. 


Per cent. 
Hsemoglobin. 




1 


20 

33 
31 

31 

24 
30 


35,600 
16,300 
26,000 
24.700 
19,700 
7,600 
14,000 
13,000 


90 

75 
80 
65 

90 

80 


February 27t]i. 
March 3d. 


2.. 


3 

4 


June 17th 


5 


" 22d. 


6 









266 



SPECIAL PATHOLOGY OF THE BLOOD. 



(9) Psoas abscess (iufected), 50,000 leufof-ytes per cubic milli- 
metre. 

(10) Abscess of ovary, 26,000 leucocytes per cubic millimetre. 

(11) Supx>uvatmg Cyst of Ovary — Midtllocular {Ganyrenc). 
Age, 52; white cells, 62,400; per cent, haemoglobin, 70, December 
22d; white cells, 89,500, December 24th. Differential count : poly- 
nuclear, 94 per cent.; lymphocytes, 6 per cent.; eosiuophiles, none. 
Autopsy. 

(12) One case of jjcrbiepliritic aMscess was watched for sonu' 
days while the patient was getting up strength for an operation. 
It was an abscess of several months' standing, not increasing in siz«' 
during the last month, and the counts, as we should exj^ect, did not 
rise or fall consideraV)ly, but showed a steady, well-marked leucocy- 
tosis. 



July 29th, 


white cells, 21,400 


" 30th. 


21,200 


agust 8th, 


22,400 


" 11th, 


23,000 


'' 24th, 


22,200. (Operation.) 



A second case counted showed only 16.000. Both abscesse> 
contained over a quart of pus. 

A third case, evidently tuberculous in origin and probably not 
much infected with pyogenic cocci, showed only 10,000 white cell> 
per cubic millimetre. 

(13) Two cases retropharyngeal abscess. Counts: Case I., 40,- 
000; case II., 30,600. 

(14) Alveolar abscess \ Case I., 19,3UU; case II., 7,500. 

(15) Abscess of the Lung — Xixe Cases. 



Case. 


Age. 


White cells. 


Per cent. 
Haemoglobin. 




1 


35 
14 

48 

9 


68,800 

30,000 

17,000 

14,000 

16,600 

7,400 

20.000 

11,900 

16,800 

16,400 

16,000 

8,400 

5,100 


80 
85 
65 

80 


Death 


2 




3 


January 9th. 

14th. 

November 7th. 

9th. 

14th. 

16th. 


4 

5 


6 








8 




9 , . 





GONORRHOEA. 
(16) Subphrenic Abscess — Four Cases. 



267 



Case. 


Red ceUs. 


White cells. 


Per cent 
haemogrlobin. 


Remarks. 


1 
2 

3 

4 


4,450,000 


3,200,000 


53. 267 
25, 600 
15, 500 
17,600 
22,000 
15,300 

13,800 
16,600 
18,000 
22, 500 


■■'55""'" 
38 


May 16th. 
May 17th. 
May 20th. 

October 20th. Supposed typhoid 

for first week. 
October 23d. 










October 27th. 
November 5th. 






November 10th. Operation; a 
quart of pus ; recovery. 







Diagnostic Value. 

1. The patient with vulvar abscess was so morbidly modest that 
she complained of all parts of her body except the one diseased, 
and gave a train of symptoms which failed to account for the leuco- 
cytosis. The presence of this leucocytosis called for a much more 
searching physical examination than would have otherwise been 
made, and the seat of real trouble was discovered. 

2. (a) The diagnosis between perinephritic abscess and cyst of 
the kidney is materially assisted by the fact that the former causes 
leucocytosis, while the latter (see page 371) does not. 

(5) Both cancer of the kidney and perinephritic abscess cause 
leucocytosis, but if fibrin is not increased cancer is the more likely 
of the two. This differential mark has served me well in two cases. 

(c) Hydatid of the kidney and pyonephrosis are not to be dis- 
tinguished from perinephritic abscess by the blood examination. In 
abscess of the lung the blood gives no information that cannot be 
more easily gained in other ways. 

3. Subphrenic abscess may be confounded with malignant dis- 
ease, both of which may cause leucocytosis; but the absence of any 
increase of fibrin speaks against the existence of an abscess. 



GONORRHCEA. 



The red cells are not affected, but in acute cases a moderate 
leucocytosis is present and fibrin is increased. Qualitatively, the 
Avhite cells have been said by Neusser and others to show an in- 
creased percentage of eosinophiles corresponding to the large propor- 



•268 



SPECIAL PATHOLOGY OF THE BLOOD. 



tion of these cells in the urethral discharge. Vorbach ' has care- 
fully studied twenty cases with reference to this point and finds 
the eosinophiles in the blood to vary from 0.5 to 11.5 per cent — 
averaging 4.2 per cent — within normal limits Bettman" and Poz- 
zoli "^ found the eosinophiles usually increased, especially when the 
posterior urethra was involved. In one case with epididymitis the 
eosinophiles numbered 25 per cent.' 

YELLOW FEVEK. 

Jones ^ found coagulation slow^ the red cells not much diminished, 
but showing decided degenerative changes; haemoglobinsemia i> 
common. He makes no observations as to the white corpuscles. 
Pothier '^ of New Orleans, studying the epidemic of 1897, found the 
following results in 154 cases : The red cells were never considera- 
bly diminished; the leucocytes varied from 4,600 to 20,000 — 
averaging about 9,000; haemoglobin usually diminished at the 
height of the disease 50 to 75 per cent; normoblasts were noted 
in a few specimens. 

A case recently observed at the Massachusetts General Hospital 
showed two days before death 7,800 leucocytes, 92 per cent of haemo- 
globin, with an absence of the typhoid serum reaction. Through 
the kindness of Dr. Pothier I have been able to study cover-slips 
from twelve cases of yellow fever from the Charity Hospital of 
New Orleans. The differential counts of leucocytes are as follows : 





I. 


II. 


m. 


IV. 


V. 


VI. 


vn. 


vm. 


IX. 


X. 


XI. 


xn. 


Polymorphonuclear n e u t r o - 
philes 


77 
18 
5 


74 

22 

2 

2 


93 
15 
2 


86 

11 
2 
.5 
.5 


87 
8 
5 


88 
4 
8 


97 
3 


84 
5 
11 


86 

4 

10 


84 
6 
6 

"4 


77 
1 


73 


Small lymphocytes 


20 
6 


Eosinophiles 

Myelocytes 


1 



Red cells showed nothing except in Case YIII., in which there 
were marked deformities and a few normoblasts. In some cases 
there was a marked leucocytosis, in others none. 



^Vorbach: luaiig. Dissert., Wurzburg, 1895. 

'^Bettman: Volkmann's Samml. kliu. Vortr.. No. 266, 1900. 

^Pozzoli: Arch, fiir Derm. u. Syph., vol. xxiv. 

■* Archives for Derm, and Syphil., vol. 49. 

5 Journal of the American Medical Association, March 16th, 1895. 

•^Pothier; J. Am. Med. As.sn., 1898. p. 885. 



MALTA FEVER. 



269 



TYPHUS FEVER. 

Ewing ^ ill four cases found no leucocytosis. 
leucocytosis, as the following case shows: 



Tumas * fouud no 





Date. 


Day of 

disease. 


Temperature, 


Red cells. 


Per cent 
haemoglobin. 


White cells. 
















A.M. 


P.M. 








January 4th 


4th. 




40.0 








" 


5th 


5th. 


39.2 


39.6 


4,440.000 


80 


9,600 


u 


6th 


6th. 


39.0 


39.5 


4,220,000 


77 


4,800 


M 


7th 


7th. 


39.0 


40.0 








U 


8th 


8th. 


39.2 


39.3 


4,280,000 


77 


3,200 


M 


9th 


9th. 


39.0 


39.5 ; 






M 


10th 


10th. 


38.8 


39.2 4,440.000 


77 


8.200 


M 


11th 


11th. 


38 3 


39.3 








ti 


12th 


12th. 


39,0 


39.2 


4,380,000 


80 


1.600 


U 


13th 


13th. 


38.8 


39.5 


4,780,000 


80 


3,200 


U 


14th 


14th. 


38.7 


39.0 








u 


15th 


15th. 


38.0 


38.7 


4,960,000 


80 


1,600 


{( 


16th 


16th. 


38.1 


38.8 








" 


17th 


17th. 


38.7 


38.6 


4,160,000 


70 


4,800 


(( 


18th 


18th. 


37.7 


38.2 








C( 


19th 


19th. 


36.6 


38.5 


3,820.000 


67 


1,600 


M 


20th 


20th. 


38.1 


38.3 








<i 


21st 


21st. 


37. 5 


38.1 


3,450,000 


62 


3,280 


" 


22d 


22d. 


38.1 


37.8 


3,450.000 


60 


8,200 


i( 


23d 


23d. 


37.5 


38.0 








M 


24th 


24th. 


37.4 


38.0 


3,130.000 


50 


8,200 


" 


25th 


25th. 


37.4 


39.3 








U 


26th 


26th. 


39.2 










Died 


on the 26th. 















On the other hand, Everard and Demoor,^ and Wilks * found 
leucocytosis. 

MALTA FEVER. 

According to the article in Allbutt's recent "Text-book of Med- 
icine " the red cells fall gradually in the course of the fever from 
5,000,000 to about 3,500,000. Bruce finds the leucocytes normal 
in most cases. (See also page 538.) Bassett Smith '" found a normal 
leucocyte count with relative increase of lymphocytes. Charles " 
makes the amazing assertion that at the height of the fever poly- 

^ Ewing: Xew York Medical Journal, December 16tli, 1893. 

•^ Arch. f. klin. Med., vol. xli., p. 363. 

^ Annales de I'lnstitut Pasteur, February, 1893. 

^Ref. in Sajous' Annual, 1895. 

5 Bassett Smith: Brit. Med. Jour., September 20th, 1902. 

6 Lancet. Jnlv 30tli, 1898. 



270 SPECIAL PATHOLOGY OF THE BLOOD. 

morplionuclear neutrophiles are entirel}- absent from the ])1(>0(1 
and only lymphocytes to be found. Musser and Sailer report a 
prolonged case with no imp(ntaiit changes in tlie blood. 

The serum reaction with the B<(cillus mdltrnsis was first oIj- 
served by Wright of Xetley and has been uniformly confirmed by all 
subsequent observers {<'.g., Musser," Curry' in twenty-six cases. 
Kretz,^ Aldridge/ Pascual/' and Bassett Smith "). The technique 
is described on page 5.38. 

Bassett Smith considers the serum reaction valuable \n prognosis 
as well as in diagnosis. His studies indicate : 

(a) If the clumping power is low, and the symptom severe, the 
outlook is bad. 

(b) If the clumping power is high and sustained the outlook is 
good. 

(c) Cases with moderate symptoms and low clumping power are 
subject to repeated relapses, grave anaemia and chronic invalidism. 

(d) Chronic relapsing cases with low but gradually rising clump- 
ing power ultimately regain full health. 

GLANDERS. 

Ohristol and Kiener " reported leucocytosis in glanders. In a 
fatal case of acute glanders with autopsy which was recently studied 
at the Massachusetts General Hospital the following counts were 
recorded : 

October 24th, 1897. Leucocytes, 13,600; haemoglobiu, 100 per cent. 

October 31st, 1897. Leucocytes, 11,600. 

November 4th, 1897. Leucocytes, 13,000. 

November 9th, 1897. Leucocytes, 12,000 

November 12th, 1897. Leucocytes, 12,400. 

Serum reaction absent; fibrin increased ; pure culture of glanders bacilh 
from abscesses ; 86 per cent of the leucocytes were polymorphonuclear : eosino- 
philes absent. 

The bacilli of glanders can occasionally be cultivated from the 
blood. 

1 Musser and Sailer: Phil. Med. Jour., 1898, p. 1408. 

^Curr}^: Jour. Med. Research, July, 1901. 

sKretz: Lancet, 1898, vol. i., p. 221. 

^Aldridge: Lancet, 1898, vol. i., p. 1394. 

^Pascual: Rev. d. Cien. Med. d. Barcelona, 1903, No. 11. 

^ Bassett Smith : Lot. cit. 

"> Comptes Rendus de I'Acad. des Sciences, November 23d. 1868. 



ACTINOMYCOSIS. 



271 



THE BUBOXIC PLAGUE. 

In 1895 Aoyonia, a Japanese observer, studied the blood of this 
disease.' He found the bacilli peculiar to the. disease by cover-slip 
preparations from the blood. Ewing ^ found them by the culture in 
90 per cent of cases near death, and in 60 per cent earlier in the 
disease (fifty cases) . Aoyoma found the red corpuscles not altered 
except that their number per cubic millimetre was at times increased 
{e.g., 7,600,000, 8,190,000). The cause of this I do not know, but it 
accounts for part of the leucocj^tosis. The white corpuscles showed 
a marked increase — 20,000 to 200,000 (!) per cubic millimetre. 
Pour cases showed counts over 100,000 and the average of six ex- 
amined was 96,600. This leucocytosis was made up almost wholly 
of polymorphonuclear leucocytes; the eosinophiles were markedly 
diminished, and the blood plates were increased. The Austrian 
Plague Commission found only a moderate leucocytosis in most 
cases. Ewing (loc. cit.) found polynuclear leucocytosis in each of 
fifty cases, but no figures like those of Aoyoma. Coagulation is 
very slow (Alice Corthorn ^). 

Curry * found the presence of a leucocytosis of practical value 
in ruling out malaria, since the plague often begins with chills and 
other symptoms suggestive of malaria. 



ACTINOMYCOSIS. 

Ewing (loc. cit.) reports leucocytosis (21,500 in a single case 
affecting the lungs, and Schmidt gives the following : 



Date. 


Red cells. 


White cells. 


Per cent 
haemogloloin. 


October 6th 


3,170", 666 

3,200,666 
2.550.000 


12,000 
14,500 
19,700 
22,900 
18.900 


35 


" loth 




20th 




" 26th 


38 


November 4th 


23 







1 " Mittheilungen aus d. med. Fac. d. Kaiseiiich Japanischen Universitat, " 
vol. iii., No. 2, Tokyo, Japan, 1895. 

2 Ewing: Med. Rec, April 4th, 1903. 

=^ Corthorn: Brit. Med. Jour., May 10th, 1902. 

4 Curry: Boston Med. and Surg. Jour., 3Iarch 21st, 1901. 



272 



SPECIAL PATHOLOGY OF THE BLOOD. 



Ill four ciises uf artiiioiuycfjsis occurring at the Massachusetts 
Geueral Ilosi^ital tlie following counts were recorded : 



Case. 


Location of tbe disease. 


Leucocytes. 


Remarks. 


1 


Liver 


31,700 
28,400 
28,200 
20,900 
23,000 
12,500 
12.200 
21,000 
26,000 


June 18th 189T 


2 


Lutigs 


" 19tli. 

" 25tli. Autopsy. 
April, 1897. 
August, 1899. Autopsy. 

AuiTusi nth. 
15th. 
17tli. 


3 

4 


Liver 

Lungs 



RABIES. 

Courmont and Lesieur ' found in three untreated cases of huiuau 
rabies an increase in the polynuclear cells, accompanied in two of 
the cases by an increase in the total count. They state that the 
'' Polynucleosis " is present from the beginning of the nervous 
symptoms, and its absence is strong evidence against the diagnosis 
of rabies. In other animals they got similar results. Their figures 
are as follows : • 



Case. 


Red cells. 


White cells. 


Polynuclear. 1 Lymphocytes. 


Hours before death. 


1 


8,300,000 


24,800 


88 per cent. 


12 per cent. 


1 


2 





increased. 


84 " 


16 - 


•5 


8 




5,000 


84 


16 


29 






7,000 


83 " ! 17 


23 






12,000 


85 


15 «' 


8 






21,000 


85 


15 


1 



In three treated cases the blood was normal. 



DENGUE 

H. Graham {Med. ^ec., February 8th, 1902) reports and pictures 
an unpigmented parasite in the blood of cases from an epidemic 
occurring at Beyrouth, Syria, His pictures are strongly suggestive 
of malarial parasites. 

TETANUS. 

In three (fatal) cases of tetanus treated with antitoxin, I ob- 
served the following counts : 

' Courmont and Lesieur- Jour, de Phys. et Path. Gen., 1901, p. 600. 



BERl-BERI. 



273 



White Cells. H£emoglobiu. 

Case I. June 21st, 1897 11,100 70 per cent. 

June 23d, 1897 11,900 

Case II 19,600 

" III October 31st 18,200 80 per cent. 

The eosinophiles do not decrease as in most fevers. 

BERI-BERI. 

In two afebrile cases seen at the Massachusetts General Hospital 
the following is recorded ; Case I.j red cells, 3,896,000; white cells, 
7,800; haemoglobin, 48 per cent. Case II., leucocytes, 25,900, 
March 6th; 10,600, March 7th; 14,000, March 16th. Differential 
count, March 16th: Polynuclear, 74.50; small lymphocytes, 18,25; 
large lymphocytes, 5.65; eosinophiles, 1.60. 

The eosinophiles are said to be much increased in the acute 
stages. Spencer ^ states there is no leucocytosis. Ewing and Daub- 
ler, each in three cases, found normal leucocyte counts with moder- 
ate anaemia and no eosinophilia.^ Wright^ records the following: 



1 18 
35 

3|18 

7130 



f>l33 



19 a5 

20 m 
2i|a5 

22 36 
33 38 
34' .. 
25 .. 
2B .. 



Stage 
of disease. 



1st week. . , 
1st week . . 
2d week . . . 
2d week . . , 
2d week , . . 
2d week . . 
3d week . . . 
4tl] week . . 

1st week . . . 
2d week , . , 
2d week . . . 
2d week . . 
3d week . . 
3d week . . 
4th week . , 
7tli week . , 
2d month., 
4th month , 



Type of disease. 



3d week . . . 
2d month.. 
8th month. 
9th month. 
10th month. 
12th month. 
12th month. 
6 years 



Acute pernicious 
Acute pernicious 
Acute pernicious , 
Acute pernicious 
Acute pernicious . 
Acute pernicious 
Acute pernicious 
Acute pernicious 



Acute 
Acute , 
Acute 
Acute , 
Acute , 
Acute , 
Acute , 



Beri-heri, residual paralysis 
Beri-beri, residual paralysis 
Beri-beri, residual paralysis 
Beri-beri, residual paralysis 
Beri-beri, residual paralysis 



Haemo- 
globin. 


Red cells. 


92 


5,430.000 


93 


5,570,000 


87 


5,100,(X»0 


86 


4,962,000 


98 


6,103.000 


92 


5,600,000 


76 


4,676,000 


83 


4,820,000 


83 


5,020,000 


95 


5,418,000 


86 


4,780,000 


88 


4,600,000 


89 


5,000.000 


89 


4,680,000 


89 


5,280,000 


88 


5,130,000 


93 


6,120,000 


89 


5,360,000 


91 


5,280.000 


81 


4,770,00<1 


93 


5,176,000 


86 


4,900,000 


92 


5,670,000 


81 


4,960,000 


92 


4,970,000 


87 


4,896,000 



White 
cells. 



Result. 



7,000 
7,200 
7,300 
7,100 
7,300 
6,850 
7,100 
7,060 

7,450 

7,400 
7,000 
6,900 
7,200 
6,820 
7,080 
7,600 
7,500 



7,200 
7.150 
6,980 
6,900 
7,600 
6,800 
6,720 
6,900 



Fatal. 
Fatal. 
Fatal. 
Fatal. 
Fatal. 
Fatal. 
Fatal. 
Fatal. 

Recovered. 

Recovered. 

Paralysis persistent. 

Recovered. 

Recovered. 

Recovered. 

Paralysis persistent. 

Recovered. 

Recovered. 

Recovered. 

Paralysis persistent. 
Paralysis persistent. 
Paralysis persistent. 
Paralysis persistent. 
Paralysis persistent. 



1 Lancet, January 2cl, 1897. 

- Bushnell has found leucocytosis in two cases (34,000 and 31,000) but 
with no increase in the percent, of polynuclears (Lancet, October 10, 1903). 

^ Wright : " Studies from the Instit nte for :Mcdical Research : Malay States, " 
vol. 11., No. 1., ^fi02. 
18 



274 SPECIAL PATHOLOGY OF THE BLOOD. 

RELAPSING FEVER. 

(See page 481.) 

(^a) Diagnosis. Leucocytosis is the rule. It is most marked 
just after the crisis. In countries where this disease is common the 
difficulty in diagnosing cases between attacks (when the spirochaetes 
are absent from the blood) is frequently met with. Lowenthal has 
perfected a method by which in most cases the diagnosis can be 
made by means of the effect of the serum of suspected cases on the 
spirochaetes of other active cases. Tlie organism cannot be culti- 
vated as yet, so that a diagnosis of this kind is possible only during 
epidemics when fresh blood containing the organism can be obtained. 
A drop of blood from the suspected case is mixed with a drop from 
a patient then undergoing a paroxysm, and the two are sealed with 
wax between slide and cover-glass and left in the thermostat for 
lialf an hour together with a mixture of normal blood and blood 
containing spirochaetes as a control. At the end of that time, if 
the case be one of relapsing fever, the organisms in contact with 
the blood from that case ('ease their motion, while those in the con- 
trol are lively. It is not a clump reaction but a direct bactericidal 
effect, which persists in the serum nearly up to the time of the next 
attack. The diagnosis so made by Lowenthal in forty cases was 
verified in every case by the course of the disease. In this way 
mild or abortive cases wnth few organisms in the blood can also be 
identified. 

{b) Prognosis. If the above bactericidal power lasts as late as 
the seventh day from the last attack, and in sufficient intensity co 
immobilize the spirochaetes in one hour or less, there will be no re- 
lapse. If these conditions are not fulfilled, relapse is sure to fol- 
low unless prevented by treatment. Lowenthal has verified this 
prognostic use of the serum in over one hundred cases. 



CHAPTER V. 

DISEASES AFFECTIiSG THE SEROUS MEMBRANES. 

Tuberculous affections of serous membranes have been dealt 
Avitb elsewhere (p. 301) ; but an exception was there made of pleu- 
risy, for although there is reason to believe that the majority of 
cases of serous pleurisy are due to tuberculosis, we rarely have proof 
of it. Tuberculous cases have not always been distinguished from 
non- tuberculous. Hence the two are necessarily considered together 
liere. 

SEROUS PLEURISY. 

Von Limbeck hnds in non-tuberculous cases from 13,000 to 
15,000 leucocytes per cubic millimetre. The red cells and haemo- 
globin are not much affected except in chronic cases. 

Eieder finds in non-tuberculous cases during the stage of fever 
moderate leucocytosis, 13,000 in one case in which the bacteriologi- 
cal examination showed the presence of Fraenkel's diplococcus in 
the exudation. After the fever has subsided the leucocytosis falls 
to, or nearly to, normal, so that cases examined for the first time 
some Aveeks after onset would show^ no increase at all. This he 
thinks explains the results of Halla and others who found no leuco- 
cytosis in serous pleurisy. According to Rieder the presence or ab- 
sence of leucocytosis depends not so much on whether the j)roduct 
is serum or pus as on Avhether the trouble is stationary or advancing. 

In tuberculous pleurisy despite fever Eieder found but 4,600 
white cells in one case, and Pick got similar results in two cases. 

Hay em makes no clear distinction of tuberculous and non- tuber- 
culous cases, and states that "acute inflammatory^' pleurisy has 
from 7,500 to 12,000 leucocytes per cubic millimetre. The fibrin 
network is much less dense than in pneumonia; in most of the tu- 
berculous cases it is not increased at all. 

Morse reports 224 counts in 20 cases of serous pleurisy — 
9 of them tuberculous. Xo relation could be established between 
the number of leucocytes and the presence, absence, or degree of 



276 



SPECIAL PATHOLOGY OF THE BLOOD. 



fever, the presence of blood or microscopic pus in the fluid, the 
amount of fluid or the duration of the ilhiess. Increase or decrease 
in the amount of fluid was not accompanied Ijy any parallel change 
in the circulating leucocytes 

Only 10 of the 224 counts were over 11,000, and 9 of these 10 
were in a single case which was shown at autopsy to be complicated 
by a secondary pneumococcus infection Morse concludes that, 
primar}' serous pleurisy does not show a leiicocytosis. His figures 
are as follows : 



From 3.0(M» to 4.000 2 counts. 

4,000 •• o.OOO 19 

5,000 " 6,000 40 " 

6,000 " 7,000 31 " 

7,000 " 8.000 5(1 " 

8,000 •• 9,000 42 " 

9,000 " 10,000 .. 27 " 

10,000 " 11.000 8 '' 

11,000 " 12,000 4 ■• 

13.000 ■• 14.000 1 

Total 224 couuts. 



Fig. 31 from Morse shows how '" the white count dodges up 
and down without the slightest apparent connection v» ith the (pian- 
tity of fluid." 

In 314 cases examined at the Massachusetts General Hospital 1 
the count of leucocytes at the time of entrance was : 





Table XXIX 


— Pleuhttic Effusion 


(SekousV 


Between 3,000 and 


4,000 


5 cases. 




4,000 " 


5.000 


14 •' 




5.000 " 


6.000 


32 " 




6,000 '• 


7.000 


37 •' 




7,000 " 
8,000 " 


8.000 


38 " 




9.000 


48 " 




9,000 '• 
' 10,000 '^ 


10.000 


36 " 




11,000 


35 " 




V 11,000 " 


12,000 


16 " 




12,000 '■' 


15.000 


31 " 


( 


)ver 15.000 




29 « 


Total 




314 cases. 


'rage 


= 9.300. 







SEROUS PLEURISY. 



277 



Here tuberculous and non- tuberculous cases are not distin- 
guishedj and a majority of them were not seen till the trouble had 
been going on two or 
three weeks. The pa- 
tients did not seek ad- 
vice until the effusion 
was large enough to 
cause dyspnoea. Of 
the 242 cases all but 
35 had no leucocytosis. 
Most of the cases were 
afebrile or nearly so. 
Eight cases reacted to 
injections of tubercu- 
lin. None of these 8 
had leucocytosis. 

The cases ivith leu- 
cocytosis were mostly 
those seen in the fe- 
brile stage, near the 
beginning of the sick- 
ness. No differential 
counts were made. 

In chronic cases the red cells are said to be considerably dimin- 
ished, but this has not been the case in our series : no count of 
under 4,000,000 was recorded, and the coloring matter was not 

much diminished. 

Summmy. 

1. Red cells and hsemoglobin show no important changes. 

2. In adults the white cells are probably never steadily increased 
as a result of simple uncomplicated serous pleurisy. Occasional 
waves of leucocytosis occur in a small percentage of cases, but even 
then the leucocyte count rarely reaches 14,000. Continuous leuco- 
cytosis indicates some complication. 

Diagnostic Value. 

The blood count may help a good deal in doubtful cases by ex- 
cluding empyema, pneumonia, and malignant disease of the lung, 
all of which are accompanied by high leucocyte counts. Compare 
the average count in serous pleurisy, 6,130, with the average in 



DAYS OF 1 
MONTH 


^S^L ^ ^^ 1* 1"^ 16 1'' 1^ 1^ ^ 21 


M. E. M. E. M. E. M. E. M. E. M. E. M. E. M. E. W. E. M. E. 
lO"'^ 






« A 1 - 




M 1 /i n 


\l-U [A A-i- 


Jl l.lj.\'^.v^. 




96° - 4- 1 1 ' ' - 4 


95° : 1 



Fig. 31. -Chart or Lefcooytes ix Plkfrisy (Morse). 



278 



SPECIAL PATHOLOGY OF THE BLOOD. 



pneumonia; 24,000, or in cnipyeiua, 18,.'>00. Tlie few counts I 
have seen of malignant disease of the hmg have been still higher. 

Hayem insists, rightly it seems to me, that clinicians could get 
real help from blood examination in almost every case of doubtful 
diagnosis in which the lung and pleura are in question. In chil- 
dren the leucocytes are sometimes considerably increased by even a 
serous inflammation, their blood reacting alwa^'s more strongly than 
that of adults to any morbid influence, and in them it may be im- 
possible to distinguish serous from purulent pleurisy. 

Ditv Plelrisy. 



8 
9 
10 
11 
12 
13 
14 



Age. 



24 

65 
24 
36 
31 
38 
21 
32 
41 
29 
25 
24 
31 
21 



Red cells. 



«'K.»^ Percent 
cells. griobin. 



30,000 

27,200 

22.200 

19.000 

16,200 

14.500 

12,000 

10,200 

9.000 

8,800 

8,700 

7,300 

7.100 

2,700 




Remarks. 



PURULENT PLEURISY (EMPYEMA). 

The counts in twenty-six cases observed at the Massachusetts 
Hospital are as follows : 

Table XXX.— Empyema. 



'^ 


Age. 


sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 
3 

4 


12 
2 

1 






h'Mim 

3,032,000 


57.800 
54.400 
55,000 
49.200 
45.500 
37,700 
31.700 
45.000 
34,000 
40.000 


51 
35 


Streptococcus. 
Pneumococci in pus. 

Fifth day. 
Eighth day. 



PURULENT PLEURISY (EMPYEMA) 



279 



Talle XXX. — ^Empyema {Continued). 













Per cent 




Q 


Age. 


Sex. 


Red ceUs. 


White 


haemo- 


Remarks. 


^ 








cells. 


globin. 




5 


4 






44,000 

24,400 
23,000 
20,000 
24,000 
31,400 
22,000 
41,500 


60 


First day. 
Third day. 
Fifth day. 
Eighth day. Tap. 
Eleventh day. 
Fourteenth day. 
Seventeenth day. 


6 


20 






41,000 
29,900 




February 11th. Tap. 
February 15th. Tap. • 


7 


21 






38,000 






8 


5 






37,800 






9 


32 


•• 




35,600 
35,200 






10 


4 




6,006,000 


34,500 
32,000 






11 


4 







30,400 






12 


47 






30,000 
39,000 
27,000 


•• 


First day. 
Third day. 
Sixth day. 








1 26,000 


' 


Eighth day. Pneumococci in pus 


13 


38 


.. 


1 30,000 






14 


26 




1,24,000 










, 21,000 










' 22,800 


45 










22,800 




June 5th. 










34,700 


. . 


June 7th. 










29,800 




June 8th. Tapped turbid serum. 










17,700 




June 9th. 










22,000 




June 10th. 










22,100 




June 12th. 










21,800 




June 14th. 










17,200 




June 22d. 










27,300 




June 24th. 










30,100 




June 29th. 










25,800 




July 8th. 










22,600 




Pneumoeoccus. 


15 


6 






21.600 
34,500 
20,600 
14,700 
11,400 
11,700 
18,000 
26,000 




Pneumococcus. 
Five days later, 
January 5th. 
January 7th. 
January 23d. 
January 26th. Tapped. 
January 30th. Re-accumulation. 
February 3d. Operated ; pneu- 
mococci and streptococci. 


16 


2 






19,600 






17 


45 






18,700 




Friedlander's bacillus. 


18 


6 






16,900 




Tap, pus. 


19 


i 24 




4,152,000 


15,000 


45 


Operated. 


20 


27 






14,200 






21 


39 






13,300 




Gangrene of lung also. 



.230 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXX. — Empyema (Continatd). 













Per cent 




6 
2 


Age 


Sex. 


Red cells. 


White 
cells. 


haemo- 
globin. 


Remarks. 










14,900 
22,800 


•• 


Fifth dav. 
Fifteenth day. 


22 


30 


. . 1 


13,000 






23 


8 


.. 1 


13,000 




Sterile. 


24 


22 






12,700 




Tuberculous. 








4,192,000 


10,800 
18,500 

14,500 
18,300 
10,000 
16,200 
15,500 
15,200 


48 
50 


December 20th. 

December 22d. Broke into luug; 

cultures sterile. 
January 2d. 
January 4th. 
January 9th. 
Pneumococcus. 








4,500,000 


14.000 












4,850,000 


12.650 
12.450 


85 
60 










4,000,000 


12,000 
11,700 
10,900 


44 


Cultures sterile. 


25 


71 






8,400 
7,600 




Three quarts sterile pus. 
Operated ; several pints of pus ; 


26 


45 






6,500 




streptococci. 



Empyema. 

Between 2,000 and 12,000 3 cases. 

12,000 " 14,000 6 

14.000 " 18.000 4 

18,000 •' 20,000 5 

20,000 •• 24,000 5 

24,000 -^ 40,000 11 

40,000 " 60,000 8 

Total 42 

Average 26,000 +. 

This is in marked contrast with serous pleurisy as above noted. 
Von Limbeck and Da Costa have noted the same thing. 

" In a case of empyema in which tubercle bacilli were extreme- 
ly niimerous, the writer found moderate intermittent leucocj'tosis 
(maximum 18,000)." (Ewing.) 

PERITONITIS. 
A patient with serous pleurisy (non-tuberculous) is hardly ever 
in danger, while if the general peritoneal cavity is the seat of a like 
inflammation J recovery is almost out of the question. 



i 



PERITONITIS. 



281 



This clinical difference is parallel to the difference in the blood 
condition; An}' inflammation (non-tuberculons) of the peritoneunij 
whether serons or purulent, calls very large numbers of leucocytes 
into the peripheral V)lood. The only exceptions to this rule are 
those cases in which the organism is so overwhelmed by the disease 
that it offers no resistance. We have seen that this same effect is 
produced in the severest cases of pneumonia and diphtheria, and 
presumalDly it is true of man}' other infectious diseases in which 
the blood has been less carefully studied. 

Almost all cases of general septic peritonitis show very marked 
leucocytosis, and the spreading of a localized process is always indi- 
cated Vjy an increasing leucocytosis. But here and there it happens 
that the patient cannot react against the disease at all, and then 
the leucocytes are normal or diminished. This never occurs in em- 
pyema, because the system is never so overwhelmed by a septic 
process in the pleura. The fibrin network is increased in almost 
all cases. The following counts, all in fatal cases, illustrate these 
points : 









Tablf. XXXT.- 


-Gexekal Peritonitis. 


No. 


Age. 


Sex. 


Red cells. 


White 

cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


34 


F. 


4.860,000 


54,000 




Abscess of spleen (?). 


2 


Adult. 


h\ 


7,000,000 


32,000 




Puiulent ; from appendix— myelocytes, 
2 per cent. 


•6 


15 






28,000 
23,000 




General septic. 
Next dav. 


4 


27 






27,800 
23,000 


68 


December 6th. Epigastric. 
December 11th. 








4,004,000 


34,200 


53 


December 17th. 


5 


28 






24.100 
17.800 





Pelvic, after abortion. Seventh. 
Fifteenth. 


6 


27 


M. 


5,317,000 


24,000 




Dysentery, with perforation. 


7 


23 


.. 




23,200 




Gastric ulcer; perforation; operation 

Death. 
Chronic, purulent. 


8 


Adult. 


F. 


4,000.000 


22,000 





9 


31 


M. 





19,000 





Ruptured bladder. 


10 


Adult. 


M. 




16,000 




Moribund. 


U 


29 


•• 




13.000 
25,800 





First day. Rupture of gall bladder. 
Second day. Died, 


12 


21 


M. 




12,200 
9,000 





June 30th. 

July 2d. Autopsy. 


13 


32 






11,000 
8,300 





October 27th. Circumscribed. 
November 2d. 


14 


26 







7,400 
9,700 




July 19th. 
July 28th. 


15 


60 






6,000 






16 


Adult. 


M. 


6,d()d,bob 


6,000 




Purulent ; operation. Death. 


17 


52 


F. 




5,328 




Obstruction; died in three days; au- 
topsy. 
Purulent. Death within 24 hours. 


18 


Adult. 


M. 


5,760,000 


5.300 




19 


41 


F. 


6.840,000 


4,600 


95 


" 24 '' 


ao 








Marked 
increase. 




After appendix operation. Diff. 1,000 
cells : Polymorphonuclear cells, 90.5 
per cent; lymphocytes, 9.5; eosino- 
philes, 0; mvelocvtes. 1. 


21 


38 


F. 




1,700! 
2,100 : 




Auaust2d. Autopsv. 
August 3d. 










1.61MI 




'i<-"pral. Gastric ulcer. 



2S2 



SPECIAL PATHOLOGY OF THE BLOOD. 



Diaynostic Valan. 

1. When a diagnosis rests between peritonitis and (a) obstruc- 
tion (non-malignant); (h) malignant disease; (c) hysteria, phan- 
tom tumors, or malingering, the presence of marked leucocytosis 
with increase of the fil^rin network syieaks stronglj- in favor of 
peritonitis. 

Obstruction or malignant disease may increase the number of 
leucocytes but rarely increases the amount of til)rin. 

Hysterical or malingering patients have normal blood. 

2. We cannot distinguish serous from purulent peritonitis in 
septic cases, but tuharruJous pcrltonifU can always be excluded if 
leucocytosis is present. 

3. As to the " chronic granular peritonitis, " non-tuberculous and 
non-septic, I have seen no reference in haematological literature and 
have no first-hand knowledge. 

4. In the troyst cases leucocytosis may be absent, as in the most 
virulent type of pneumonia. 

PERICARDITIS (WITH EFFUSION). 

As in most other inflammations of serous membranes, we can dis- 
tinguish the tuberculous cases which have no leucocytosis from the 
rheumatic or septic cases which always increase the white cells. 
The tuberculous cases are discussed under tuberculosis (see page 
288). The following counts illustrate the rhemnatic form of the 
disease : 

Table XXXIl. 









White 


Per cent 




i 


^r 


Red cells. 


cells. 


hsemo- 


Remarks. 


O 


< 






Rlobin. 




1 






42,400 
32,600 
19,200' 
17,500 




November 3d, 1895. 

November 7th, 1895. 

November 11th, 1895. 

December 8th, effusion nearly gone. 


2 




2,632,000 


21,600 

27,100 
36,600 
26,700 
19,200 

24,800 
28,600 
20.100 


45 


December 24th, endopericarditis, 

chronic nephritis. 
December 26th. 
December 29th, no fever. 
May 1st. 
May 3d. 
May 4th. 
May 7th. 
Mav 8th. 



PERICARDITIS (WITH EFFUSION). 



283 



Tabi.e XXXII. {Continued). 



10 



11 21 



Red cells. 
4,568,000 

4,168,060 

4,376,666 
4,296,000 



Wbite 


Per cent 


cells. 


hasmo- 




globin. 


26,000 


67 


19,400 





24,000 




19,447 


67 


15,400 




14,600 


65 


12,000 


63 


17,680 


58 


12,500 




13,400 


52 


13,900 




15,800 


53 


12,600 


68 


6,300 


62 



Remarks. 



December 14th 
December 20tli, 



Autopsy. 
Tapped. 
February 28th. 
March 3d. 
December 26th. 
December 30th. 
January 15th. 
February 9th. 



effusion subsidiuo- 



Hayeiii has noted that pericarditis is far more apt to produce 
leucocytosis than is endocarditis. 



Dry Pericarditis. 





White 


Per cent 




y. 


?-, Red cells. 1 'leils 


haemo- 


Remarks. 






globin. 




1 


11 




34,600 


80 


Adhesions. Autopsy. 


2 


39 




31,800 
18,600 
22,000 


80 


March 31st. 

April 9th. 

April 22d, dry pleurisy, death. 


3 


11 




20,600 
25,000 


86 


March 12th. 

March 13th, general septicaemia, pleu- 
risy with effusion, alcoholism. Au- 
topsy. 


4 


15 




11,800 

19,900 

1,850 

16,900 


76 


February 5th, mitral regurgitation, 
February 7th, cardiac hypertrophy 
February 15th, perinephritis. 
February 27th, enlarged liver, ascites. 



H^MOPERICARDIUM. 



White cells. 


Per cent 
haemoglobin. 


Remarks. 


13,000 
14,200 


70 


August 20th, tapped ; bloody fluid obtained 

discharged well. 
August 22d. 


10,400 




August 24th. 


15,100 




August 27th. 


7,200 




August 28th. 









284 



SPECIAL PATHOLOGY OF THE BLOOD. 



MENINGITIS. 

Leucocytosis is usually well marked. Von Limbeck considers 
that tuberculous meningitis can be distinguished from purulent by 
the absence of leucocytosis in tuberculous cases, but Osier ' states 
that many cases of tuberculous meningitis do have leucocytosis 
throughout their course, and my own observations (see Table 
XXXIII.) confirm this. Of Rieder's cases one had leucocytosis 
and one did not. Zappert's case had 11,130 white cells, and 
Ziemke had one with 17,500. It seems, therefore, that we some- 
times have here an exception to the rule that tuberculous processes 
do not produce leucocytosis. Certainly some cases do follow this 
rule. But however this may be, it is certain that purulent menin- 
gitis, whether secondary or of unknown origin, is characterized by 
high leucocyte counts, and if in a case evidently of meningitis of 
some kind leucocytosis is absent, the case is probably tuberculous in 
origin. 

Table XXXIII. — Meningitis — Of Various Types not Epidemic. 



d 

12; 


Age. 




Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


19 






62,000 




Autopsy ; pneumococcus. 


2 


Adult. 


M. 


siooo/obb 


40,000 




Diff. 1,000 cells: adult cells, 93 
per cent; young cells, 7 per 
cent ; eosinophiles, 0. 


3 




M. 


6,400,000 


33.000 


. . 


(Otitis?) question of typhoid. 


4 


■'*38'" 







33,000 
36,400 


90 


February 13tli. 
February 17tli, death. 


5 


1 







33,000 


90 


Cerebro-'spinal ; death. 


6 


23 


ii. 


6,'66o,boo 


27,500 
16,500 


95 


March 16th; cerebro-spinal. 
March 18th. 


7 


37 







27,000 




Autopsy ; pneumococcus ; otitis 
media purulenta. 


8 


48 


•• 




25,600 


80 


Subacute cerebro-spinal; March 

2d. 
March 5th. 










22,000 












24,600 




March 9th. 










26,200 




March 13th. 










31,400 




March 16th. 










26,000 




March 19th. 










27,400 




March 21st. 










22,000 




March 27th. 










28,000 




March 30th. 










26,400 




April 3d. 










27.600 




April 6th. 



I 



Pi'actice of Medicine," 2d edition. 



MENINGITIS. 



285 



Table XXXIII, — MENrNGiTis— Of Various Types not Epidemic {Gontiiiued) 













Per cent 




^ 


Age. 


« 


Red cells. 


White 


hseuio- 


Remarks. 


^ 




^ 




cells. 


Rlobln. 






■■ 




18,600 




April 10th. 










10,400 




April 13th. 










7,600 




April 16th. 










8,600 




May 14th. 


9 


20 






23,200 

18,400 
14,300 
12,800 
8,000 
10,000 
10,000 


63 


December 14th ; cerebro-spinal. 

December 22d. 

December 24th. 

December 26th. 

December 28th, 

December 30th. 

January 1st 


10 


15 






22,000 
19,000 
20.000 
38,000 
32,000 
26.000 
27,000 
22,000 
24.000 
26,000 
27.400 
25,500 
20.000 


68 


July 27th; cause unknown, 

July 29th, temperature 102.2° 

July 31st 

August 3d , temperature 103°. 

August 5th 

August 7th. 

August 9th. 

August 12th. 

August 13th. 

August 18th. 

August 19th. 

August 21st. 

August 26th. 

Death September 5th ; no autopsy. 


11 


36 







20,800 


75 




12 


4 






19,800 
19,900 


62 


Autopsy ; pneumococcus. 


13 


15 mos. 


F. 


5,020,000| 19.500 


73 




14 


32 




1 19,000 


85 


Cerebro-spinal: April 11th. 










13.000 




April 16th. 










28,400 




April 23d. 










31,200 




April 26th. 










18,000 




April 29th. 










11,200 




May 2d. 


15 


34 






18,500 




Cerebro-spinal 


16 


4 


• • 


• • • 


16,400 


64 


Lumbar puncture shows diplo- 
coccus intercellularis of Weich- 
selbaum. Death. 


17 


7 


M. 





16,000 






18 


26 


M. 




16,000 






19 


20 


F. 


, i . , , . . . 


15,784 


. . 


Autopsy ; cerebro spinal 


20 


^ 


M. 




14,200 




Basilar ; no tuberculosis in family ; 
had pneumonia. 


21 


22 


M. 


4,356,000 


14,000 


72 




22 


27 






13,200 
15,600 


85 


Cerebro-spinal, Mai'ch 28th. 

Death, March 30th 

Different couuts 500 cells , polynu- 
clear leucocytes, 83,8 per cent: 
small lymphocytes. 11.4 per 
cent; large lymphocytes, 4 8 
per cent. 



286 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXIIl — Meningitis — Of Vakiuis Typks not Eimj)emic {Continued) 



i 


Age. 


1 


Red ceUs. 


White 
cells. 


TVr cent 

llU'IllO- 

erlohin. 


23 

24 
25 

26 

27 


10 

35 
40 

32 
16 


M. 







12,800 
18,600 
10,000 
11,700 
9.600 

8.000 
7,200 


85 

70 
95 



lleuiarks. 



Jainuirv 24tli. 
Janujiry 26th. 
February 3d, 

Autopsy; chronif diffiis)^ pacliy- 

incnintjitis. 
Cerobro-spinal ; death. 



EPIDEMK^ CEHEBUO-SPIXAL MKXIX(JITIS. 

Williams Hiids bnicocytosis in about two-tliirds of liis cases. 

The followiug counts were made during the epidemic of 1897. 
The red cells are not markedly affected. Vasomotor polycythaemia 
may occur. Leucocj'tosis is the rule, but is not invariable. In u 
general way the higher the count the severer the case, and the count 
usually rises as the case gets worse and falls with improvement, 
though often very slowly. In the febrile recrudescences so common 
in chronic cases, the leucocytes usually rise again, though the eosin- 
ophiles may not disappear as the}' ordinarily do in the earliest 
daj^s of the illness. Ko prognostic inferences can be drawn from 
the behavior of the eosinophiles in meningitis. 

Table XXXIV. — Epidemic Cerebko-Spinal Meningitis. 

White Cells. Counts. 

Between 5,000 and 10,000 9 

10,000 " 15,000 50 

15,000 " 20,000 42 

20,000 " 25,000 27 

25,000 " 80,000 21 

30,000 " 35,000 9 

35,000 " 40,000 ... 10 

40,000 " 45,000 7 

45,000 " 50,000 1 

50,000 " 55,000 5 

Total 181 

Flexner and Barker, investigating a large epidemic at Lonacon- 
ing, Md., found leucocytosis in every case (12,000-32,000 per cubic 



EPIDEMIC CEREBRO-SPINAL MENINGITIS. 287 

millimetre). The epidemic studied by Williams ami myself was 
apparently due to the diploeoccus iutracellularis of Weichselbaum. 
Secondary meningitis (otitis media, etc.) seems to have similar 
effects on the blood. 

Dlagnostw Value. 

Meningitis is the only intracranial disease (except abscess and 
apoplexy) Avhich shows leucocytosis, and this fact may be of great 
help in excluding other causes of coma. 

1. Brain tumor, hysteria, lead encephalopathy, and most cases 
of narcotic or alcoholic intoxication do not cause leucocytosis and 
hence can be excluded by its presence. 

2. Uraemia, apoplexy, sunstroke,^ diabetic coma, and post- 
epileptic coma may have leucocytosis and cannot be distinguished 
from meningitis when leucocytosis is present; but the absence of 
leucocytosis excludes meningitis. 

3. Some cases of typhoid, when seen for the first time and with- 
out a history of the previous illness, may be difficult to distinguish 
from meningitis, but typhoid never has leucocytosis if uncomplicated 
and meningitis always has. 

4. From pneumonia we cannot distinguish meningitis by the 
blood count. 

^ lu a case of heat exhaustion (temperature 104°) without coma, a leucocj'te 
count of 27,200 is recorded at the Massachusetts General Hospital. 



PART III. 

CHRONIC INFECTIOUS DISEASES. 



CHAPTER VI. 

TUBERCULOSIS. 
Agglutixative Eeactiox. 

Since Arloing and Oourmoiit's conimimication iu 1898 at least 
nineteen other observers have studied the question whether there is an 
agglutinative reaction between the blood of tuberculous patients and 
tubercle bacilli dissociated in hsh bouillon or other nutrient liquids. 
Their results have been admirably summarized by L. M. Loeb.^ 
Thirteen of the nineteen observers (Russian, French, and German) 
get results practically identical with those of Arloing and Courmont, 
i.e ., find agglutination in a considerable percentage of tuberculous 
subjects and also in from 30 to 60 ^yer cent of those showing no dinical 
evidence of tuberculosis. This last fact deprives the test of practical 
value in the estimation of Loeb and of some others whose results 
are the same as those of Arloing and Courmont. 

At least six investigators, among whom are Beck, Koch, and 
Fraenkel, fail altogether to confirm Arloing and Courmont's results. 
I have no personal experience with the test. 

Red Corpuscles and Hemoglobin. 

(a) Quantitative Changes. 

I. The striking fact is the absence of such ansernia as we should 
expect, judging from the pallor of the patients and the nature of 
the disease. It is common to find a normal or even increased num- 
ber of red cells in pale, cachectic-looking consumptives. We cannot 
help wondering whether our methods of examination are at fault, 

' Loeb. Jour. Am. Med. Assn., May 33d, 1903 (Hterature). 



TUBERCULOSIS. 289 

that is, whether the drop we examme is typical. (For discussion 
of the subject see page 68.) However this may be, it is undoubt- 
edly the fact that in most cases of tuberculosis, even in advanced 
stages, the count of red cells is often normal, or increased lulth cor- 
respondingly high hmnioglohin. 

II. In a smaller number of cases the hsemoglobin is much di- 
minished, although the count of red cells is normal — in other 
words, we find the blood characteristic of a moderately severe sec- 
ondary ansemia. The red cells are numerous enough, but only 
because their numbers have been recruited by the influx of ^' half- 
baked " or decrepit corpuscles, small-sized and pale, poor in albu- 
min and haemoglobin. 

The condition differs from that of chlorosis mainly in that some 
of the red cells are normally developed and nourished, while in 
chlorosis all, or nearly all, are feeble. Such blood occurs in the 
severer and more cachectic sufferers from tuberculosis, just often 
enough to make us wonder that it is not always to be found. 

III. In a small percentage of cases both red cells and haemo- 
globin are considerably diminished, the latter usually suffering 
more than do the actual number of cells, that is, the color index is 
usually below 1. 

Von Limbeck ' has recorded a case in wliich in the course of a 
tuberculous process (acute) the red cells fell as low as 700,000 
(white cells, 6,000; specific gravity 1.032). But the account of the 
blood is not sufiiciently explicit in this case to enable us to exclude 
a true pernicious anaemia in the course of which the tuberculosis 
may have been only the last incident. No other such case is on 
record, so far as I am aware. 

"In phthisis, as well as in other tuberculous processes, great 
caution must be used in judging of the patient's improvement 
from an increase in red cells or haemoglobin. The writer has seen 
the haemoglobin and red cells increase while the patient was rapidly 
losing flesh, the lesions advancing, and the total quantity of blood 
doubtless falling. In several of Bierfreund's cases the haemoglobin 
steadily increased while the patient was developing general tuber- 
culosis." (Ewing.) 

IV. Fibrin is not increased unless extensive secondary infection 

is present. 

^ Loc. cit., p. 564. 
19 



290 SPECIAL PATHOLOGY OF THE BLOOD. 



(b) Qualitative Cltanges. 

I There may be none whatever. 

II There may be only a pallor of some of the individual corpus- 
cles with slight changes in size and shape. 

III In very severe cases the poikilocytosis may be extreme, but 
this is much rarer than in many other cachexias of the same severity 
(^e.g , malignant disease) 

IV^ An important point is the usual absence of nucleated red 
cells Even after hemorrhages it is rare to hnd any nucleated red 
cells, and this is in marked contrast with cancer cases, in which 
nucleated red cells are the rule. 

V, The degenerative changes described by Maragliano are some- 
times found in severe cases with mixed infection (vide infra). 

As regards the influence of the different seats of tuberculous 
disease (meningeal, pulmonary, genito-urinary, acute miliary, etc.) 
upon the red corpuscles and haemoglobin the following are tlie 
probabilities: 

Pure tuberculous disease itself, whatever its seat, has little or no 
effect upon the blood The widely different conditions of the blood 
found in different cases depend probably on the presence or absence 
of various other organisms (diplococcus lanceolatus, pyogenic cocci) 
associated with the tubercle bacillus, and on whether there is some 
drain on the body albuminoids (diarrhoea, peritoneal effusion, star- 
vation, prolonged suppuration). When the infection is a mixed 
one, the blood shows the ordinary effects of septicaemia (for then 
the case is practically one of septicaemia) in lessening the number 
and quality of the red cells. When there is drain on the fluids and 
proteid constituents of the body, the red cells may not seem to lie 
diminished, owing to the concentration of the blood from loss of 
fluid Under such circumstances they may even seem increased, 
but the individual corpuscles are sure to be lacking in haemoglobin 
and the other nitrogenous bodies of which they largely consist. 

Fever may be present without there being any changes in the 
red cells that we can detect. It is only septic fever, and not the 
fever of pure tuberculosis, that drains the corpuscles of their vitality 
and lowers their numbers. 



PHTHISIS. 291 

Leucocytes. 

(«) Quantitative Changes. 

Here, as with the red cells, the strikmg fact is the absence of 
changes in pure tuberculosis It makes no difference whether we 
are dealing with tuberculosis of the bones, serous membranes, or 
internal organs. So long as the infection remains unmixed the 
white cells are not increased. In certain localities (lungs, kidneys) 
the opportunities for a secondary infection and septicaemia are so 
great that we frequently find evidence of it in the blood On the 
other hand, psoas abscesses before they are opened often contain 
only tubercle bacilli, and the blood of such cases shows no consider- 
able changes. 

So much more is knoAvn of the numerical variations of the leuco- 
cytes in tuberculosis than of the other blood constituents, that I 
shall give a separate account of them in phthisis, in tuberculous 
bone disease, in tuberculous meningitis, acute miliary tuberculosis^ 
genito-urinary tuberculosis, and tuberculous peritonitis 

I, PHTHISIS. 

I In inci2jient 2)htJiisis the leucocytes are normal except after 
haemoptysis. 

II, After attacks of luemoptyiils^ there is usually leueoeytosis, 
subject to wide variations according to the amount of the hemor- 
rhage and the resisting power of the patient This follows the 
laws of ordinary post-hemorrhagic leueoeytosis {i-ide supra) and dis- 
appears quickly when the hemorrhage ceases 

III. Cavities. — Very constantly accompanied by leueoeytosis. 
Indeed the absence of leueoeytosis in any case proves the absence of 
any cavity of considerable size. 

Ewing " has seen both lungs consolidated and riddled with small 
cavities in a case lasting five weeks, yet the leucocytes were never 
found above 12,000 The absence of leueoeytosis in these cases of 
acute phthisis, which resemble pneumonia, may often be of value 
in diagnosis. Similarly, in a case of subacute empyema in which 
the tubercle bacillus was largely concerned, the leucocytes were? 
found not to exceed 14,000 during an acute febrile period." In 
moderately advanced cases living in the open air with ample proteid 



292 SPECIAL PATHOLOGY OF THE BLOOD. 

diet, Galbraitli' finds '^moderate leucocytosis, large absorptive lym- 
phocytosis, and an almost constant eosinophilia." 

IV. Extensive infiltration (" tuberculous pneumonia "j may 
cause marked increase of white cells, sometimes as great as in 
croupous pneumonia, but this is not invariable, 

y„ Fibroid Fhthisis (chronic interstitial pneumonia;. — As a riilt- 
the leucocytes show no increase, but if, as sometimes occurs, we 
have the combination of tliis condition with cavity formation, the 
latter may increase the count of white cells. 

VI. Fever. — When the temperature is normal, the leucocytes 
are normal, but a febrile state may or may not be accompanied by 
leucocytosis (according, presumably, as the fever is or is not due to 
pyogenic organisms). 

VII. Tuberculin Injections. — At the height of the reaction fevei' 
the leucocytes almost always rise, the lymphocytes and eosinophiles 
being relatively increased. 

In a general way, the worse the case the higher the leucocyte 
count, yet the signs may be advanced without causing any leuco- 
cytosis if cavities are absent. 

The following tables give some idea of the range of the counts 
in average hospital cases of phthisis : 

Phthisis — Red Cells. 

Between 2,000.000 and 3,000,000 = 1 case. 
3.000.000 " 4,000,000 = 22 cases. 
4.0()0.0(M> " 5,000,000 = 27 " 
5, 000. 000 " 6.000,000 =17 •' 

Total 67 -" 



I 



Put in 


SIS— 


-IL 


E.MOGLOF.IN. 


rom 10 to 20 


per 


cent 


- 1 case. 


" 20 " 


30 




" 


= •' 


" 30 " 


40 




a 


= 5 cases 


" 40 " 


50 




" 


= 8 " 


" 50 '^ 


60 




" 


= 21 " 


" 60 " 


70 




(( 


= 35 •' 


" 70 '' 


80 




ii. 


= 38 " 


" 80 " 


90 




a 


= 19 " 


" 90 " 


100 




a 


= 5 " 


Total. 








. 132 '' 



'Galbraith: Brit. Med. Jour., March 14th, 1903. 



PHTHISIS. 293 



Phthisis— White Cells. 

Between 3,000 and 4,000 = 5 cases. 

4,000 •' 5,000 = 7 •' 

5,000 " 7,000 = 25 " 

7,000 " 9.000 = 26 " 

9,000 " 11,000 = 27 " 

" 11,000 " 15,000 = 48 " 

« 15,000 " 20,000 = 29 " 

" 20,000 " 30,000 = 14 " 

" 30,000 " 40,000 =: 4 « 

Total 185 '• 

The number of those sliowing leucocytosis is slightly greater than 
those without it, probably because incipient cases rarely think them- 
selves sick enough to come to a hospital. On the other hand, some 
of the cases which appear to have been going on for months have 
normal leucocyte counts. The duration is less important than the 
nature and severity of the process. It is rare to see extensive signs 
in the lungs without leucocytosis — fibroid phthisis excepted. 

Qualitative Changes in the White Cells. 

1. Many cases show none at all. 

2. When the leucocyte count is normal we may find an increased 
percentage of large and small lymphocytes, such as is commonly 
found in any blood ]30or in nutritive qualities (see page 89) . 

3. When leucocytosis is present, we usually find the ordinary 
marked increase in the percentage of polymorphonuclear cells at 
the expense of the lymphocytes. 

For example : C. D , male, thirty-two years old. Tubercu- 
losis of lungs, with cavities; leucocytes, 17,580. Differential count 
of 1,000 cells shows : 

Per cent 

Polymorphonuclear 834 

Lymphocytes ( small) 8. 2 

Large lymphocj^tes (large and transitional) 8.4 

Eosinophiles 

4. Eosinophiles are increased during the reaction from an injec 
tion of tuberculin, and also in some cases with cavities in which 
possibly the individual inoculates himself with tuberculin manufdCt- 



294 _ SPECIAL PATHOLOGY OF THE BLOOD. 

ured ill the cavities of his own lungs. In most cases associated 
with leiicocj^tosis the}' are absent. 

5. ]\Iyelocytes were found by Holmes, \V. E. May, and myself 
in many cases of advanced phthisis. They averaged 0.3 ijer cent. 

Ofhi^r CluiiKjas. 

Neusser and liis followers have advanced a theory that the occur- 
rence of perinuclear basophilia ' during tuberculosis is a favorable 
sign and marks a system capable of resisting the tuberculous infec- 
tion The researches of Futcher and my own attempts to verify 
Neusser's theory have not confirmed his findings. 

Holmes, of Denver, has studied the leucocytes in phthisis with 
great care and considers that he finds therein means not only of 
diagnosing tuberculosis by the blood alone, but of measuring the 
degree of advancement of the process and the amount of resisting 
power in the patient. 

I have carefully followed out Holmes' procedures with stains 
seen and approved b}' him. J can verify most of his statements of 
fact, but some of the inferences which he draws therefrom are, I 
think, whoU}^ unwarranted The blood changes in pulmonary tu- 
berculosis are mainl}- such as he describes, but they have no diag- 
nostic value, as similar changes are found in a great variety of other 
diseased conditions. The increase of polymorphonuclear forms in 
advanced cases, the increased amount of "debris," the degenerating 
forms, etc , are all characteristic not of tuberculosis alone, but of 
au}^ severe suppurative process. The increase of "debris" is proba- 
bly the same datum which Watkins interpreted as an increase in 
blood plates and Goldberger and Weiss as "extracellular glycogen." 
(With Holmes' " undeveloped nuclei " in the leucocytes, compare 
page 102 ) 

II. BOXE TUBERCULOSIS. 

Brow^n- has studied seventy-two cases, Dane ^ forty-one. Dane's 
study of the blood in forty-one cases of hip disease and Pott's dis- 
ease is a very careful one. Whenever abscesses appeared in con- 
nection with the disease, cultures were taken when the abscess was 
first opened and again later on, and the coincidence of low counts 

^ See Appendix. 

'^ Transactions of California 3Iedical Society, 189T. 

s Boston Medical and Surgical Joarnal. :May 28tli, 1896. 



BONE TUBERCULOSIS. 295 

with absence of pyogenic cocci and with high counts of secondary 
pyogenic infection is very notable. Dane's conckisions are as 
follows. 

1. " High leucocyte counts, especially in hip disease, point to 
the probability that there is, or soon will be, abscess formation; 
but low counts do not preclude the presence of abscess, especially 
in long-standing cases. 

2. " If abscess is present, a low count of white cells indicates 
the absence of secondary pyogenic infection (proved by cultures). 

3. " Cases of traumatic origin are generally accompanied by a 
high leucocyte count. 

4. " The leucocyte count bears no direct relation to the tempera- 
ture; one case with 30,980 leucocytes (five-year-old girl) showed a 
temperature of only 99.4° at the time of the count. In another 
girl of three years whose temperature ranged between 101° and 
104°, the leucocytes were only 7,224, or subnormal for that age 
{ride mfrU, page 512). 

o. " Cases where at the primary operation the pus proved sterile 
show an increase in the leucocyte count when the wound becomes 
infected with pyogenic organisms" (as it always does). 

6. " The red cells are rarely diminished, but the haemoglobin is 
usually relatively low" (mild secondary anaemia in these cases). 
This absence of a diminution in the red cells in these cases is the 
more remarkable because they were almost all in young children 
whose blood is much more sensitive to any deleterious influence than 
that of adults." 

Brown dissents from several of Dane's conclusions. He thinks 
that a case may go on to abscess formation without any increase in 
the leucocyte count When an increase does take place, he thinks it 
due eitlier to a secondary infection or to an increased activity of the 
tuberculous process itself without any secondary infection The 
latter process, however, in Brown's experience causes only a moder- 
ate increase (2,000-3,000), while if a marked increase suddenly or 
gradually occurs he thinks it " most significant of secondary infec- 
tion." With Dane's fifth conclusion he wholly agrees and adds: 
" After the infection (produced by the operation) the leucocytosis is 
very high for a time, and if the sepsis is acute and threatens life, it 
remains high until the crisis is passed." Otherwise it gradually 
falls after the first few days, and if the patient progresses w^ell, it 
disappears. If the pyogenic matter overcomes the recuperative 



296 SPECIAL PATHOLOGY OF THE BLOOD. 

power, the leucocytes fall as in peracute pneumonia or peritonitis. 
In such cases the anaemia increases as well. 

Qualitative Changes. 

(a) As in other forms of tuberculosis there may be none at all. 

(b) The cell-changes in purely tuberculous cases are illustrated 
well by Case 17 of Dane's series, a boy of seven whose blood on th«^ 
day of operation for hip disease with large abscess showed 8,932 
leucocytes. The differential count was as follows: 

Per cent. 

Polymorphonuclear neutrophiles 40 

Small lymphocytes 49 

Large lymphocytes and transitioual forms 8 

Eosinophiles 3 

Eight ounces of pus were evacuated, in which cultures showed 
the absence of pyogenic organisms. 

This case demonstrates that some cases of tuberculous suppura- 
tion have no tendency to produce leucocytosis or to increase in the 
neutrophiles, but influence the blood only by producing what might 
be termed a functional debility of the blood through lack of nuti-i- 
tive substances in the plasma. This condition is by no means pecul- 
iar to tuberculosis, but occurs in a great variety of debilitated or 
cachectic conditions, as already stated. 

(c) But when a septicaemia complicates the tuberculosis, cell 
metamorphosis appears to be accelerated, and we get with the 
quantitative increase of leucocytes such qualitative changes as the 
following : 

Per cent. 

Polymorphonuclear neutrophiles 84 

Lymphocytes (small) 9 

Lymphocytes (large and transitional) 6 

Eosinophiles 1 

This was a case (No. 33 of Dane's series) in which the abscess, 
sterile when first opened, had become inoculated with the staphylo- 
coccus aureus. 

(d) Not every case with leucocytosis shows qualitative changes 
as the above. One of Dane's cases (No. 22, a boy of seven) showed 
a leucocytosis of 23,387, but only sixty per cent of these were poly- 
mo7*phonuclear and two per cent eosinophiles. 

In a case recorded by Dane (No. 32), tuberculous osteomyelitis 



BONE TUBERCULOSIS. 



297 



showed 6,083 white cells (subnormal, as the child was only two 
years old) with sixty-four per cent of polymorphonuclear cells. 
The pus from the bone cavity showed no pyogenic organisms on cul- 
ture. Ordinary septic osteomyelitis gives very different results (see 
page 265). Dane's cases were almost exclusively hip and spinal 
affections. 

The following cases from the Massachusetts General Hospital 
records illustrate tuberculosis of other bones : 



Table XXXV. 



Case. 


Diagnosis. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


1 
2 

3 

4 


Tuberculosis of the knee-joint 

Tuberculosis of the knee joint , 

Metatarsal tuberculosis 

Tubercular rib 


6.472,000 
2,704,000 
4,650,000 
5 016 000 


9,400 
8,000 
6,500 
5,800 


63 

61 
73 











III. ACUTE MILIARY TUBERCULOSIS. 

Probably there are no important changes in the red cells or hae- 
moglobin. The number of cases on record is too small to enable 
me to speak positively on this point, but the acuteness of the dis- 
ease would lead us to expect the normal or approximately normal 
conditions recorded in the few published cases. 

About the leucocytes we know more. 

Quantitative Changes in the Leucocytes. 

There were normal or subnormal counts in two-thirds of my 
cases. Sometimes the count is raised by a complicating pyogenic 
infection or by an extensive involvement of the meninges. In other 
cases the cause of the leucocytosis is obscure. 

Warthin ^ reports a case with autopsy in w^hich he made over 
thirty counts of the white corpuscles, verifying the more remark- 
able results by repetition. Autopsy showed, besides miliary 
tuberculosis, a cavity in the lower lobe of the right lung and a 
suppurating focus about the seminal vesicles containing four 
ounces of pus rich in tubercle bacilli. Whether pyogenic orgaii- 



1 Medical News, 1895. 



'298 



SPECIAL PATHOLOGY OF THE BLOOD. 



isms were also present is not stated. The leucocyte counts were 

as follows : 

Table XXXVI. 



Day. 


Hour. 


Leuco- 
cytes. 


RfMuark 


s. 


December 6th 


10 a.m. 


3.500 






12th 


8 A.M. 


5,000 






18th 


5 P.M. 


3,500 






22d 


10 A.M. 


5,625 






22d 


11:30 a.m. 


4,725 






22d 


3 P.M. 


5,000 






22d 


5 P.M. 


3,125 






24th 


8:30 A.M. 


3,750 






24th 


11:30 A.M. 


3,750 






24th 


2 P.M. 


2,500 


« 




24th 


4:30 p.m. 


2,500 






25th 


8 A.M. 


1,875 






28th 


5 30 p.m. 


3,750 


Red cells, 4,125,000; 


haemoglobin, 80f^ 


29th 


10 a.m. 


1,250 






29th 


2 P.M. 


1.250 






29th 


5:30 p.m. 


3,750 






31st 


12 m. 


1,250 






31st 


6 P.M. 


2,500 






January 2d 


11 a.m. 


1,250 






2d 


5 p.m. 


2,500 






3d 


2:30 p.m. 


600 


Severe chill. Count 
times. 


repeated several 


5th 


8:30 a.m. 


3,750 






5th 


11 A.M. 


3,137 






5th 


4 P.M. 


8,125 


Moribund. 




6th 


9 A.M. 


10,000 






6th 


10 a.m. 


5,625 






6th 


11 A.M. 


2,500 






6th 


12 M. 


5,625 






6th 


12: 50 P.M. 


Death. 







In another ease he found also a subnormal count. Eieder found 
normal counts in two cases. Von Limbeck states that the leuco- 
cytes are normal, but gives no counts. 

The following cases from the Massachusetts General Hospital 
records illustrate these points : 



TABLE XXXYH.— Acute Miliary Tuberculosis. 



6 


•< 
28 


:sex. 
M. 


Red cells. 


White 
cells. 


Per cent 
hgemo- 
globin. 


Remarks. 


1 


2,448,000 


550 
1,200 
7,100 


35 


March 8th. 
March 11th. 

March 11th, gave protonuclein gr. xv. 
t.i.d. 



ACUTE MILIARY TUBERCULOSIS. 



299 



TABLE XXXVII.— Acute IMiliary Tuberculosis {Continued). 





i 


Sex. 


Red cells. 


White 

cells. 


Per cent 
haemo- 


Remarks. 


z; 


< 








goblln. 










3,296,000 


1,300 
3,000 


43 


March 13th, differential count: 
Polvmorptionuclear, 78 per cent. 
Lymphocytes (small), 13 
Lymphocytes (large), 9 ^ 
Eosinophiles, 1 

March 14th, glands rapidly diminish- 
ing. 

March 18th, died. Autopsy. 


2 


57 
24 




4,424,000 


2,200 
2,200 
4,700 
7,100 
3,300 
8,000 
4,400 
9,100 


85 


August 20th. 
August 25th. 
August 27th. 
August 29th. Autopsy. 
First day. 
Third day. 
Ninth day. 
Twelfth day. 


3 


52 


F. 




3,500 


90 




4 


18 


M. 




3,600 




Autopsy. 


5 


40 


M. 




3,750 


w 


Autopsy. 


6 


40 






4,000 






t^ 


14 


F. 


3,*72d,00b 


4,400 


45 


Autopsy. 


8 


26 


•• 




4,600 
3,400 




First week. 
Sixth week. 


9 


51 


M. 


4,664,000 


4,800 




Autopsy. Chronic phthisis also. 


10 


23 


M. 





4,900 




Autopsy. Differential count normal. 


11 


14 






5,400 


65 




12 


18 


F. 




5,400 
7,400 


80 

•• 


September 21st 

September 24th. No serum reaction. 


13 


29 


M. 




5,600 


64 


Autopsy. No serum reaction. 


14 


12 


F. 




6,100 




Autopsy. 


15 


19 


F. 




6,600 




Autopsy. 


16 


56 






6,800 

8,200 

21,000 




First day. 
Ninth day. 
Day of death. 


17 


37 


F. 




1,500 


n 


Autopsy. 


18 


18 


•• 




7,600 
8,600 




First day. 

Fourth day. Ninth, death. 


19 


36 


M. 




7,600 




Healed phthisis also. Autopsy. 


20 


36 




4,' 784, 000 


7,600 

8,200 
7,200 


70 


January 26th, differential count: 
Polymorphonuclear, 62 per cent. 
Lymphocytes, 37 "• 
Eosinophiles, 1 

January 29th. 

January 31st. Autopsy. 




20 


F. 




7,800 
7,200 




May 14th. 

May 22d, death. Autopsy. 


21 


29 






7,600 


100 


September 25th. 


22 


35 




3,*926,00b 


8,000 
8,900 


45 


November 12th. Autopsy. 


23 


22 






8,600 


75 


Tuberculous salpingitis ; tuberculous 
meningitis. 


24 


30 




4,500,000 


8,800 


52 




25 


24 






9,100 


85 


August 24th. 



300 SPECIAL PATHOLOGY OF THE BLOOD. 

TABLE XXXVIL — Acute Miliary Tlberculosis {Contiaued). 



z 


5 

< 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 




30 

45 
38 
28 
22 
20 


M. 
M. 

M. 




14,000 

21,200 

8,600 

9,000 

9,250 

9,450 

10,000 

12,200 

12,200 

12.700 

13,200 

20,000 

20,200 

20.900 

24.700 


65 

80 


August 25th. 

August 26th. 

August 28th. 

August 31st. 

April 18th. 

April 20th. Autopsy.' 

Autopsy. 

Autopsy. 

Death. 

Phthisis also. Autopsy. 

March 15th. 

March 16th. 

March 17th. 

March isth. 

March 2(iih. Autopsy. Tuberculous 


26 
27 

28 


5 


237,000 


30 






31 
32 

33 


21 
6 

20 

44 

78 

14 


•• 




16,000 
19,800 
30,200 
22.000 
25,500 
27,000 
30,000 
32.000 

36,000 


85 
83 

55 
90 
29 


meuiugitis. 
Autopsy. 
October 29th. 
October 31st. 
Noveml)cr 1st. 
November 3d. 


34 
35 

36 


2,'4i6,000 


Death. 

Ditferential count 1.000 cells: 

Polynudear, S7 i>er cent. 

Lymphocytes, 11 

Eosinophiles. n 

Myelocytes. ~' 

Normoblasts - •'). 

Megaloblasts - 2. 
Complicated with diphtheria. 
Autopsy. 




■* i 



Case 1 of the above table is a striking example of the remark- 
ably low leucocyte count sometimes seen in this disease The counts 
were carefully verified by several competent observers. 

Qualita tice Chan ges 
In Warthin's case above quoted, he repeatedly made differential 
counts of the leucocytes by Ehrlich's methods, ^vith this average 
result : 

Polymorphomiclear neutrophiles 91.48 per cent. 

Lymphocytes (small) 3.52 

Lymphocytes (large and transitional) 3.00 

Eosinophiles 0.00 " 

Myelocytes 2.00 " 

The differential counts made in four of my cases showed no con- 
stant percentages. 



TUBERCULOSIS OF SEROUS MEMBRANES. 



301 



lY. TUBERCULOSIS OF SEROUS MEMBRA^'ES. 

1. TuBEEcrLOvs Peritoxitis. 

The blood condition is exactly as in other forms of tuberculosis, 
except in so far as it is modified by the drain exerted on the blood 
by diarrhoea or by transudation or exudation into the peritoneal 
cavity. Such events concentrate the blood by withdrawing water 
and albumin from it and may give us a normal number of red cells 
per cubic millimetre, when in reality a considerable aueemia is pres- 
ent. As a rule, the blood shows a mild secondary anaemia without 
leucocytosis or with leucopenia. This is exemplified in the follow- 
ing table from the Massachusetts General Hospital records : 

Table XXXYIII. 





: 




^Yhite 


Per cent 






^ 


h 1 Sex. 


Red cells. 


cells. 


haemo- 


Remarks. 




z 


< I 






globin. 






1 


26; F. 


3,120,000 


2,240 


58 






2 


28 
33 






2 600 

3.800 


48 






3 


F." 


2,'966,000 




4' 24 31. 


5,360,000 


3,800 




January 6th, 1896. 




i 


5.760,000 


5.600 


85 


April 13th, 1896. 




Oi 25 


F. 




3,900 




Tuberculous tube. 




6 21 


31. 




4.400 








7 25 




.... 


4,700 


52 






8 21 




3."684.000 


4,800 


43 






9 27 

1 


mV 





4,900 
5.500 


64 


March 1st. 
March 9th. 




10; 43 


M. 




5,000 




December 18th. 1895. 




i 




4;.566,00b 


3,250 


76 


January 10th, 1895. 




iiiso 


F. 




5.180 




Tuberculous tube. 




12| 20 


F. 


5!936,00b 


5,400 








131 28 






5,400 
5.530 




Pleuritic effusion also. 




14 44 





2;974,bb0 




15 i 24 






5.600 
5,600 








16 34 








17 16 


F. 


3!846,bob 


6,000 








18 33 


F. 


4.000,000 


6,000 








19 37 






6,200 














5,400 








20 3 





6.008,000 


6.200 


45 






21 50 


F. 


5,240,000 


6.400 








22 13 






6.400 
6.700 


55 


May 22d. 1896. 




23 37 


M. 






24 '>i 




3,'552.bbo 


6.800 


45 






25 30 


mV 


5,560.000 


6.800 








26 15 




5,112.000 


6,900 


70 


Polynuclear, 44 per cent ; 
49 per cent ; eosinophl 


lymphocytes. 
es 7 per cent 


27 44 


F. 




7.000 


73 






28,19 






7,200 
7,300 


52 


April 18th. 




29 37 




4,' 556,000 





302 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXVIII. {ConiinuefT). 



i 




Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


RO 


16 
15 
23 
26 
33 
31 
17 
48 
32 
20 
29 
16 

15 
19 
50 
41 
20 
38 
47 
21 
19 
37 
5 
19 

15 
19 

16 

27 
6 

11 
16 




4,616,000 
4.050,000 
3,880,000 
3,960,000 


7.400 

7,400 

6,800 

7.400 

7,900 

8,000 

8.000 

8.000 

8,200 

8.500 

8,600 

8,700 

7,600 

9.800 

9.800 

10,000 

10.000 

10.800 

11.200 

11,300 

11,500 

11.600 

12.400 

14.200 

14.500 

11,600 

14,600 

16.000 

14.000 

16,100 

14,200 

11,000 

16.900 

18,300 

18,000 

31,900 

18,500 

22,900 
18,200 
18.600 


56 
50 
52 

47 
70 

45 

75 
60 

58 
30 

50 

65 
65 

50 

80 

1 
1 

76 
52 

45 1 

60 ■ 

85 


April 25th. 
May 5th. 
May 10th. 
May 20th. 


81 








8'^ 








33 


M. 


4,368,000 




35 
86 

87 


mV 


4,*964,00b 




38 
39 
40 
41 


F. 
F. 
F. 


4' 200, boo 

3,400,000 


Tuberculous tube. 

First (lay. 
Thirtieth day. 


40 






43 

44 
45 
46 

47 
48 


F.' 

'f.' 


4,"6o6,boo 

5,200,000 

4,"8i6,bbo 




49 
50 


F. 


3,555,000 




51 
52 
58 





4*472,000 




54 








55 






March 24th. 


56 






3Iarch 26th. 
First day. 


57 
58 

59 


F. 


4,576,000 


Sixth day. 
Eighth day. 
Pelvic abscess also. 

Intestines perforated. 

Ninth daj^, after two dry taps. 

Thirteenth day, pus and fcieces coming 

through tap holes. 
Seyenty-eighth day. Autopsy. 


60 

















J 



I know of few differential counts of leucocytes in tuberculous 
peritonitis. 



TUBERCULOSIS OF SEROUS MEMBRANES. 



303 



2. Tuberculous ^Eexixgitis. 

Kemarkably few counts are on record so far as I can ascertain. 
Von Limbeck gives but a single case (with, autopsy). Four counts, 
the last on the day of death, showed the following : 

May 22d, 1889 : Leucocytes 8,000 

" 23d, 1889: " "^ 8,000 

" 24th, 1889 : " 6,000 

" 26th, 1889: " 7,500 

E-ieder records two cases, in one of wliich the leucocytes were 
"normal or subnormal, in the other increased." In both diagnosis 
was confirmed by autopsy. The counts in these cases were as fol- 
lows: 

Case I. —February 26th, 1891 : Leucocytes „ 7,800 

March 2d, 1891 : Leucocytes , 5,900 

Case II.— May 30th, 1891 : Leucocytes 14,400 

Ttirck studied three cases, all showing more or less leucocytosis 
(9,600 with 90 per cent polynuclears and no eosinophiles, 17,100 
and 18,100 with 83 per cent polynuclears and no eosinophiles, 20,800 
with 86 per cent polynuclears and no eosinophiles). Blood plates 
and fibrin were not increased. 

Pick saw two cases : 

Case I.— February 28th, 1890: Leucocytes 6,500 

March 5th, 1890 . Leucocytes 8,000 

In the second case there was also no leucocytosis. Autopsy in 
both. Sorensen's ' two cases showed respectively 8,300 and 9,400 
leucocytes. My own results in forty-three cases are as follows : 

Table XXXIX, — Tuberculous Meningitis. 



d 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


1 






ri9 acta 


70 

70 


0, 


2 

1 






31,000 

29,900 
29,000 
51,000 


8 













Remarks. 



April 30th. 
May 8d. 
Death, May 5th. 

February 21st. 

February 26th. Autopsy. 



Cited by Rieder 



304 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table XXXIX.— Tuberculous Meningitis {Contiuu&l). 



i 


Age. 


Sex. 


Red cells. 


White 
cells. 


Perce 
haem< 
globir 


"^ Remarks. 
1. 


4 


2i 


M. 




28,000 
84,800 


63 


July 8th. 

July 9th. Autop.sy. 


5 


9 mos. 






27,000 






6 


2 


F. 




25,900 
23,800 

82.800 
27,800 
23.600 
16,500 
21.000 
19,800 




May 30th. 

June 4th. Tuberculous peritonitis 

also. 
June Hih. 
June lOih. 
June 12th. 
|June 14th. 
June 16th. 
June 18th. 


7 


11 


.... 




24,800 
82,700 
82,600 




First day. 
Third day. 
Fifth day. Death. 


8 


5 







24,000 
17,000 




August 28th. 
August 30th. 
Bronchopneumonia. Death. 


q 


9 
34 






22,400 
21,500 


80 


Death. 


10 


M. 




Autopsy. 


11 


3 






20.400 






r^^ 


10 mos. 






19.500 
17,600 
16,400 






18 


9 mos. 








14 


10 mos. 






Temperature 103' F., tirst day. 










29.500 




Death, fifth dav. 


15 


3 

3 

23 






15,600 
15,400 
15.300 
20,000 


55 
90 




16 









17 






December 1st. 








December 3d. 










41.000 




December 4th. 
December 5th. Death. 


18 


13 






15.050 
20,500 


80 


February 9th. 








February 21st. 










25.000 




February 23d. Death. 


19 


35 


M. 





14.700 


68 


Pleurisy also. 


20 


22 


M. 





14.400 
19.400 
13.200 
19.800 




January 25th. 
January 30tli. 
February 2d. 
February 6th. Autopsy. 


?,1 


6 






14 000 




First day. 










18.000 




Fifth day. 


22 


6 






13.900 




First day. 










21.400 




Fourth day, temperature 102' F. 










17,400 




Tenth day. 


28 


46 






18,900 


80 


Death. 


94 


11 






13,500 
11,800 


80 


April 3d. 
April 18th. 




















12,200 




April 20th. 


y.i 


5 






13,400 
13,100 
12,200 


75 


Death 


'^fi 


3 
23 






95 




27 






Noyember 5tli. 










16,200 




. No y ember 7th. 



TUBERCULOSIS OF SEROUS MEMBRANES. 



305 



Table XXXIX — Tuberculous Meningitis {Cojitinued) . 



1 


Age. 

12 

8 

U 
35' 

18 

10 
lOmos 


Sex. 


Red cells. 


''S 






'>S) 






so 






31 






3'' 






33 
3^ 







35 






36 
37 


22 

30 . 
45 
5 

40 

24 
20 

31 


.... 





38 
39 


M. 




40 






41 
42 

43 


F. 


4,590,000' 
4,792.000 









White 
cells. 



16,700 
14,000 

12,000 

11,500 

11,900 

11,000 

10,800 

10,500 

10,000 

11,000 

9,400 

9,200 

8,200 

13,300 

8,100 

8,000 

7,500 

7,000 

10,000 

6,600 

6,100 

6,200 

6,300 

2,000 

3,200 

2,600 

29,300 



Per cent 
haemo- 
globin. 



65 

80 

96' 



50 



Remarks. 



November 10th. 
November 12th. 
November 13th. Death. 

First day. 
Fourth day. 
Death. 

Temperature 107" F. Death. 
First day. 
Fourth day. 
Death. 

First day. 
Seventh day. 



First day. 
Fourth day. 

November 28th. 

November 30th. 

December 3d. 

December 6th. Death. 

May 29th. 

May 31st. 

June 5th. 

June 10th. 

June 12th. Death. 



In thirty-two of my forty-three cases there was leucocytosis, 
sometimes very marked. 

Hoagland, of Colorado Springs, found in four cases the foUow- 
iu.a:: 



Case. 


Age. 


No. of days 
before death. 


White cells. 


Per cent 

poly- 
niiclears. 


Per cent 
lympho- 
cytes. 


Per cent 
eosino- 
philes. 


Per cent 
myelo- 
cytes. 


1 
2 
3 
4 


3 
2 
4 
3 


10 
14 

18 
12 


18,000 
28,000 
16,000 
29,000 


87 
90 
83 

82 


12.5 

9 

16.7 

17.0 


0.5 

1.0 

.3 

.5 


0.0 



0.0 

.5 



Tlie red cells and haemoglobin show, as a rule, but slight changes, 
as is so often found in other forms of tuberculosis. The absence 
20 



306 



SPECIAL PATHOLOGY OF THE BLOOD. 



of any increase in fibrin is, Tiirck thinks, of some diagnostic value 
in excluding other types of meningitis. 

It seems therefore that pure tuberculous meningitis differs mark- 
edly from other pure tuberculous processes, in that it has a strong 
tendency to raise the leucocyte count. Osier's results point to the 
same conclusion. ' Ziemke '^ has recently reported a case with 17,500 
leucocytes per cubic millimetre. 

3. Ti KERcuLous Pericarditis. 

In one case in which tubercle bacilli were repeatedly demon- 
strated in the fluid obtained by tapping the pericardial sac I found 
no leucocytosis. The counts in two others are shown in the accom- 
panying table. I have not met with any other reports on the blood 
in this condition. 



Case 


Age. 

19 

48 


Sex. 


Red cells. 


White cells. 


Per ceBt 
haemoglobin. 


Remarks. 


1 
2 




4,728,00*0 


6,200 
7,000 


60 





4. Tuberculous Pleurisy. 

No doubt a large proportion of all pleuritic effusions are tubei- 
culous in origin; and, so far as I have seen, no high counts are re- 
corded in cases proved by culture or inoculation to be tuberculous. 
The low leucocyte counts in most pleurisies (see page 276) tend 
to show that they are tuberculous and not due to pyogenic organ- 
isms. 

Pick mentions that he finds no leucocytosis in tuberculous pleu- 
risy when uncomplicated by phthisis, but reports no actual counts. 



5. Glaxdular Tuberculosis. 

In cases of so-called scrofulous glands, whether in children or 
adults, the blood shows no important changes except that in chil- 
dren the hsemoglobin may be considerably diminished. 

^ "Text-book of Medicine," 3d edition. 
■^Deut. med. Woch., April 8th, 1897. 



TUBERCULOSIS OF SEROUS MEMBRANES. 



307 



Glandular Tuberculosis. 



No. 


Age. 


Sex. 


White cells. 


Per cent 
haemoglobin. 


1 


20 

28 

7 


F. 
M. 
F. 


5,600 
10,900 
11,000 


75 


2 


65 


3 









Leucocytosis is absent unless an abscess has been opened and 
infected. Whether or not tuberculosis of the abdominal or other 
internal lymph glands affects the blood, I am unable to say, 

6. GElSflTO-UniNARY TUBERCULOSIS. 

Here the opportunities for a secondary pyogenic infection are so 
good that in about one-fourth of the cases we find the blood of sep- 
ticaemia present. The following cases, all involving the bladder, 
kidney, and the external genitals, illustrate this point : 

Table XL. 



No. 



4 
5 
6 

7 

8 

9 

10 

11 



Age. 



40 



65 



50 
23 
6 
30 
23 
31 
40 
41 

26 



Sex. 



M. 



Red cells. 



3,796,000 



3,588,000 

3,000,000+ 

4,564,000 

3,532,000 
3,632,000 



White 
cells. 



29,200 

20,800 
20,200 
21,800 
25,600 
29,600 
42,400 
38,000 
25,600 
23,600 
28,000 
26,600 
20,100 
15,100 
15,000 
14,452 
12,600 
11,000 
10,400 
10,400 
14,452 
10,400 

11,300 



Per cent 
haemo- 
globin. 



65 



65 



58 

62 
44 

55 
50 



40 

40 

38 



Remarks. 



December 9th, Ren mobilis; tu 

berculous laryngitis. 
December 10th. 
December 15th, 
August 6th. 
August 10th. 
August 11th. 
August 13th. 
August 17th. ■ 
August 19th. 
August 21st. 
August 24th. 
August 28th, death. 



T. B. in urine ; kidney operated. 



Bladder. 
Kidney. 



T B. of right kidney with pleu 

risy ; March 18th. 
March 25th. 
April 9th. 



308 



SPECIAL PATHOLOGY OF THE BLOOD. 



TaKLE XL. {Contimitih. 



No. I Age. Sex. Red cells. 



White 
cells. 



Per cent 
haemo- 
plobin. 



Remarks.. 



12 
13 
14 
15 
16 
IT 



22 
27 
56 
32 
9 
64 



18 33 

19 35 
8 

22 
43 
42 



20 
21 
22 
23 

24 31 

25 27 

26 31 i F 

27 42 ^>l 



3.320.000 



3,624,000 
3,492,000 
3,712,000 
3,936.000 



F.' 
F. 


5.808.66(» 



11,300 



,500 



10,200 

10.100 

10,100 

9.70(1 

9,4(Mi 



40 



43 
3.5 
43 
47 



April 16th, differeutial couut : Pol- 
yuuclear. 87.8 per cent; small 
lymphocytes, 7.4 percent ; large 
lymphocVtes, 3.6 per cent ; 
eosinophiles. 1.2 percent. 

April 27th. 

Mav 11th. 

Mav 19tli. 

MaV 2stli. 



Testicle an«l luuir. 



! 9,300 




I 9,000 




8,800 


6-5 


8,500 


70 


8,400 




7,800 


80 


7,600 


90 1 


7.600 


57 


7.400 


m\ 


6,900 


60 : 


' 7,000 


. . ■] 


8.700 




' 8.300 





KidiR'V. Di-ath. 



December 18th. 
December 26tli. 
Janiiarv lltli. 



SYPHILIS. 

Eeiss, in an aiticle in the Arrhlc f. I)^^ruwtitlu<ih' ami S(jphUU, 
1895, Heft 1, says tliat the general constitutional influence «>f tht- 
poison of syphilis is best indicated by the condition of the l»lon. 
In one hundred cases he has arrived at the following conclusion^ 
regarding the 

lied Cells and Haemoglobin. 

During the time between the chancre and the secondary symp- 
toms, the red cells are slightly decreased, but this is much more 
marked after the appearance of secondary symptoms and continues 
for a time even after treatment has begun. The hemoglobin sinks 
steadily from the time of the primary lesion on, but is not espe- 
cially affected by the eruption. Even under treatment the haemo- 
globin necer gets quite up to normal and prolonged mercurial treat- 



SYPHILIS. 



309 



ment lowers it, altliough mercury has at first a beneficial effect on 
the haemoglobin as well as on the other constituents of the blood. 

Konried ' goes further into detail. According to him, in the 
first four to seven weeks after infection, the number of red cells- 
remains normal, but the hsemoglobin begins to fall off, losing from 
ten to twenty per cent in that time. Afterward it sinks steadily 
until treatment is begun, the number of corpuscles also falling 
slightly. 

Newmann and Konried ' reporting in 1893 on two hundred cases, 
say that up to the time of the secondary symptoms from twenty-five 
to thirty per cent of haemoglobin is generally lost, without much 
change in the red cells, which sink considerably in number after 
the outbreak of secondary lesions. Lezius ^ likewise finds no diminu- 
tion in the numher of red cells until the outbreak of secondary 
lesions. 

Ewing says : " With the outbreak of secondary symptoms the 
red cells begin to fall rapidly, reaching in untreated cases as low as 
2,000,000 or less (Konried). In ten cases Wilbouche witch found 
an average decrease of 229,000 cells daily. At the same time the 
haemoglobin continues to diminish and may fall to 55-25 per cent 
within a few weeks or months." 

All these changes, like those about to be described, are apt to 
be more marked in women than in men. In cases going on to the 
secondary stage untreated, the haemoglobin may sink to as low as 
twenty-five per cent. In the tertiary stages and in hereditary and 
so-called " constitutional syphilis " the red corpuscles are much more 
seriously affected, diminishing considerably in number as well as in 
weight and color. The hereditary syphilis of infancy may indeed 
produce fatal anaemia and very low counts are common, with large 
numbers of nucleated red cells and great deformities in shape and 
size. 

The effect of mercurial treatment on the red cells is interesting. 
Gaillard^ found that the count of red cells increased during the first 
fourteen days, and the haemoglobin during the first twenty-four 
days of treatment. After that time, if mercury was still given, the 
haemoglobin and later the number of corpuscles began to decline. 

Konried (loc. clt.) found the haemoglobin to rise during the ad- 

^ Internatioual Dermatological Congress, 1892. 
'^ Wiener klin. Wocli., 1893, ^o. 19. 
sjnaug. -Dissert., Dorpat, 1889. ^Gaz. des Hop., 1885, No. 74. 



310 SPECIAL PATHOLOGY OF THE BLOOD. 

ministration of the first twenty-five to thirty-five inunctions, after 
which it began to go down. This was in cases in which treatment 
was begun just after the onset of secondary symptoms. In the 
worst cases it sank even as h)w as forty-five per cent despite treat- 
ment, and this usually means a bad prognosis and severe tertiary 
symptoms to come. In one of my own cases the haemoglobin was 
only thirty-seven per cent, though the red cells Avere 4,988,000 
(color index, 0,37). 

Ewing says : " In one the spleen was much enlarged and con- 
tained gummata, while the blood showed the lesion of grave sec- 
ondary anaemia, with a tendency toward the microcytic type and a 
low haemoglobin index. In other cases the abundant megalocytes 
with increased haemoglobin closely resembled those of pernicious 
anaemia." 

Potassic iodide increases the red cells and luemoglo1)in, but has 
no special effect on the leucocytes. 

Cases often show spontaneous improvement in their anaemia as 
well as in other symptoms. 

Justus ~ in five hundred cases claims to have observed, in sev- 
enty to eighty per cent of all cases of syphilis, a peculiar reaction 
of the haemoglobin, wliich does not occur in any other disease and 
which he considers of much diagnostic value. 

According to him, if in cases in which secondary symptoms 
have not yet appeared, we test the haemoglobin and then give an 
inunction or a subcutaneous injection of mercury, we find that with- 
in twenty-four hours a very marked fall in haemoglobin has taken 
place (ten to twenty per cent), owing to the action of the mercury 
on the weakened corpuscles. This sudden fall is followed by a 
gradual rise until within a few daj^s the coloring matter is at a 
point slightly higher than before the mercury was given. In dis- 
eases other than syphilis this sudden drop does not occur. After 
the advent of secondary symptoms the peculiar reaction to mercury 
does not occur. My own experience with the test is small. In nine 
cases of active syphilis I found it present. In three inactive 
cases and in thirty-five control cases of various other diseases it was 
absent. In a case of chlorosis the reaction was positive. 

Brown and Dale ^ studied thirteen cases of syphilis, and con- 
cluded that the test is unreliable and of little practical value. In 

1 Justus: Deut. Arch. f. klin. Med., vol. 75. 
^ Cincinnati Lancet-Clinic, March 24th, 1900. 



SYPHILIS. 311 

some of their cases the drop in haemoglobin did not a^jpear until 
several inunctions had been given. 

Jones ^ examined thirty-five syphilitics and eighteen control 
cases. Of seventeen cases of active syphilis thirteen gave positive 
results. Jones thinks the test of some value in diagnosis though 
by no means pathognomonic. 

Christian and Foerster (^University Medical Magazi7ie, Novem- 
ber, 1900) studied twenty-nine cases and found the test quite un- 
reliable. They obtained positive reactions in neurasthenia and two 
cases of chancroid. On the whole I agree with their conclusions. 

White Cells. 

1. Here the changes are not characteristic. In the first stage 
the leucocytes are either normal or slightly increased, but the per- 
centage of polymorphonuclear forms is almost always notably low 
and that of the lymphocytes high. If mercury is given at this 
stage, the polymorphonuclear forms begin to increase toward nor- 
mal, and the lymphocytes proportionately to decrease. [Mercury 
given to healthy persons has just the opposite effect, increasing 
the lymphocytes at the expense of the polymorphonuclear forms.] 
Iodide of potassium works exactly like mercury in this respect, in- 
creasing the polymorphonuclear leucocytes in syphilis, while it 
diminishes them in healthy persons. 

2. As the eruption breaks out leucocytosis (12,750 and 16,800 
in two of my cases) sometimes appears, the proportion of lympho- 
cytes usually being increased. Various writers have reported an 
eosinophilia at one or another stage of the disease, but Peter, ^ who 
has carefully studied this point, states that eosinophilia is never 
produced by syphilis at any stage, though from various causes the 
eosinophiles may be temporarily increased. Engel describes a 
syphilitic child in whom the percentage of polymorphonuclear cells 
steadily rose as the child got worse. In such cases Engel considers 
these cells to be of prognostic importance. P. K. Brown has made 
a similar observation in bone tuberculosis. Treatment with mer- 
cury and potassium iodide tends to bring down the count of lympho- 
cytes, and to increase the polymorphonuclear forms, while it raises 
the count of red cells. 

In the tertiuTij stages, with the severe anaemia which is often 

1 New York Med. Jour., April 7tli, 1900. 

2 Peter: Dermat. Zeit., 1897, vol. iv., p. 669. 



312 



SPECIAL PATHOLOGY OF THE BLOOD. 



present, there occur occasionally leucocytosis, not uncommonly ^vith 
small percentages of myelocytes, and a marked lymphoc3^tosis. 
Miiller ' has described four cases of anaemia in syphilis so severe as 
to simulate pernicious anaemia very closely. In one the red cells 
sank to 720,000. Laache'^ mentions a similar case. 

There are no constant changes in the blood plates. They are 
often increased in anaemic cases and are in all probability the bodies 
described by Losdorfer as specific and characteristic of syphilis 
(See discussion by Vomer. ^) The specific gravity follows pretty 
closely the haemoglobin percentage 

Didf/iiostic I'ft/i/c. 

Justus' reaction of syxDhilitic blood to mercury, if true, would 
be of great value in distinguishing early syphilis from various other 
causes of debility, but it is in all probability useless. 

The chief value of the blood examination in syphilis is not for 
diagnosis but as a measure of the stage and severity of the infec- 
tion. Low haemoglobin and high percentages of the lymphocytes 
are characteristic of severe types. Leucocytosis usually means that 
the case has got beyond the primary stage, while in the tertiary 
stage the presence of myelocytes with a marked anaemia is of serious 
import. 

Certain cases of this last type may closely resemble pernicious 
anaemia, from which, however, they are to be distinguished by their 
low color index, the frequent presence of leucocytosis, and the rel- 
ative infrequency of megaloblasts as compared with the normo- 
blasts, in case nucleated red cells are present. 

Table XLI. — Syphilis. 













Per cent 




.\0, 


Age. 


sex. 


Red cells. 


Wbite cells. 


globin. 


Remarks. 


1 








24.000 


70 


Meningitis. 


2 


80 






24,000 


90 


Cerebral. 


8 


81 







18,600 




Tertiary. Liver? 


■4 


27 






16,500 
12,700 




Hemiplegia. 
Eleventirdav. 


5 


25 






15,900 


80 


Cerebral. 


6 


11 






15,200 
15,130 


75 


Cerebral. June 4th. 
June 8th. 



' Charite-Annalen, vol. xiv. - Loc. cit. 

Vomer: Deut. med. Woch., December 11th, 1902. 



LEPROSY. 
Table XLI. — Syphilis {Continued). 



313 











Per cent 




No. Age. 


Sex. 


Red cells. 


White cells. 


hgemo- 
globin. 


Remarks. 








13,400 




June 14th. 


1 






14.260 




June 21st. 


7 1 30 






15,000 




Temperature 100°, with iritis. 


8 


45 






14,800 




Cerebral. 


9 


11 






14,400 


72 


Cerebral. 


10 


23 






14,200 


80 




11 


40 






13,200 




Cerebral. 


12 


59 






12,600 


88 


Cerebral. 


13 


31 






12,100 


70 


Secondary. 


14 


24 






11,300 


80 


Cerebral. 


15 


36 






10,350 


65 


Cerebral. 


16 


48 






9,700 




Cerebral. 


17 


53 


.... 




9,400 


ioo 


Cerebral. 


18 


29 




5,880,600 


8,640 


52 


Amyloid liver and spleen. 


19 


33 






8,600 






20 


51 






8,400 


100 


Liver. 


21 


66 






7,960 


81 


Cerebral. 


22 


28 






7,600 


65 


Tertiary. 


23 


31 






7,200 






24 


35 




5,280,000 


6,900 


55 


Myocarditis ; larynx. 


25 


40 






6,600 


70 


Cerebral. 


26 


49 






6,500 






27 


38 






6,000 


65 




28 


70 






6,000 


85 


Tertiary. 


29 


24 






5,600 


70 




30 


32 






4,500 




Testicle. 



Dr. Thomas J. Yarrow kindly sends me a blood report of the 
following case, apparently of hereditary syphilis : 





Dec. 12tli, 
1898. 


Dec. 
20tli. 


Jan.4th, 

1899. 


Jan. 
27th. 


Remarks. 


Red cells 

White cells 


3,350,000 
20,000 










Polynuclear 

Lymphocytes. . . 
Eosinophiles 


35.0^ 
44.6^ 
20.6^ 


26.7^ 
54.4$^ 
18.7^ 


39.8^ 
52. % 

8. % 


52.8^ 

43.8^ 

3.4^ 


The blood changes here re- 
ported coincided with the 
use of mercury and with 
the disappearance of the 
anaemia and of all symp- 
toms. 


Normoblasts 


60 per 
c.mm. 









LEPROSY. 

Winiarski (Fetershurgev medielnische Wocheuschrift, 1892, p. 
►65) gives a careful study of seventeen cases of leprosy, and P. K. 



314 SPECIAL PATHOLOGY OF THE BLOOD. 

Brown ' has watched sixteen cases. They find in young persons 
with mild cases no changes from the normal blood. 

In severe cases, especially in old xjeople, the anaemia may be 
severe (2,290,000 red cells with 54 per cent of haemoglobin) and 
even comparable to pernicious anaemia (1,989,000 red cells with 
63 per cent of haemoglobin). In anaemic cases the color index is 
•apt to be high, in one case it was 1.7 (!). Such severe types 
are associated with an increase of the average diameter of the red 
cells, which exj^lains the high color index. The haemoglobin was 
relatively low in any case. 

Lfnirocjjfps. 

No increase was 2^''^se)it in any case. Four cases were subnor- 
mal. The percentage of lymphocytes, as in other debilitated con- 
ditions, is often high (forty-five to forty-seven per cent). Eosinf>- 
philia has been recently noticed by Bensaude,- by Achard and 
Loeper^ (five to eleven per cent), and by Sabrazes and !Mathes,* the 
latter only in nodular cases and not in those of the anaesthetic type. 

Bacteriology of the Blood. 

Brown has succeeded in demonstrating the leprosy bacillus in 
the blood of one-half of his cases. The bacilli appear for the most 
part within the leucocytes, and here they accumulate in large num- 
bers. It is especially in the tubercular form of the disease that 
Brown has found them. He was unable to cultivate the bacillus. 

Streker ' has likewise found the bacillus in the blood of four 
cases. 

^ San Francisco County Medical Society, July 13th, 1897. 
'■^Bensaude: Ref. in Presse med., 1898, p. 306. 

^Achard and Loeper: Ref. in Brown's article in Internat. Clinics, vol. iv., 
12th series. 

^Sabrazes et Mathes: Gaz. Hebd., 1902, No. 2. 
^Streker: Miinch. med. AYoch., 1897. Nos. 39 and 40. 



PART IV. 

DISEASES OF SPECIAL ORGANS. 



CHAPTER VII. 

DISEASES OF THE DIGESTIVE APPARATUS. 

1. . Mouth. 

Ill a case of tlirush complicating chronic nephritis the following 
counts were recently recorded at the Massachusetss General Hospi- 
tal: October 16th— red cells, 5,000,000; white cells, 16,200; 
hsemoglobiii, 52 per cent. October 24th — white cells, 13,800; hse- 
moglobin, 55 per cent. 

2. (Esophagus (see Malignant Disease, page 439). 

3. Stomach, Displacements of the organ (gastroptosis) have 
no effect upon the blood. 

The conditions existing in the stomach may influence the blood 
profoundly in three ways : 

(<f) They may be such as to prevent the normal absorption of 
nitrogenous material on which the blood, like all tissues, is abso- 
lutely dependent. Then the blood becomes starved. The extreme 
of this condition is the so-called "atrophy of the gastric tubules," 
which may produce fatal anaemia. In lesser degrees the same proc- 
ess is at work in many forms of chronic dyspepsia, gastritis, or 
chronic starvation. 

(h) They may lead to severe and repeated hemorrhages. 

(c) They may lead to an auto-intoxication which poisons the 
blood as well as other tissues. 

On the other hand, it is probably through the influence of an 
altered blood serum on the duodenal mucous membranes that ulcer 
of the duodenum is a sequel to severe burns of the surface of the 
body. 

For an account of the influence on the blood of digestion, inges- 
tion of liquid, and starvation, see page 90. 



316 SPECIAL PATHOLOGY OF THE BLOOD. 

DISEASES OF T H !•: S T O M A C 11. 

ANOREXIA NEKVOSA. 

From pure starvation the red cells may get as low as 900,000, 
as in the case mentioned by Martin. In the early stages the blood 
is normal A recent hospital case showed 8,900 leucocytes witli 87 
per cent of haemoglobin. 

GASTRIC CANCER. 
(See Malignant Disease, page 43:>.) 

GASTRIC ULCER. 
lied C'fd/s < 1 11(1 Ild-iiHH/lohln. 

A severe anaemia is common. Out of the 51 cases in Table 
XLIL, A, 42 — 80 per cent — had less than ;50 per cent of haemo- 
globin, and of the 51 in which the red cells were counted, 17 liad 
under 8,000,000 red cells per cubic millimetre. The average count 
of red cells at the time when treatment began was 3, .372,000. 
There is no single disease, so far as I am aware, in which the red 
cells are so apt to be so low, exee])t pernicious anaemia. Even can- 
cer, as a rule, does not fall so low. This is due mosth", I think, 
to the frequency of hpinorrhfujo from the ulcer; it is uncommon to 
see marked anaemia in patients who nave never had a hemorrhage. 

This anaemia is all the more striking when we remember that 
the frequent vomiting from which most patients suffer tends tr> 
concentrate the blood, increase the number of cells in a drop, and 
so to make the blood seem less anaemic than it really is. This ten- 
dency to concentration is probably effective in some of the cases 
observed especially by Oppenheimer,' in which despite great j^allor 
he found normal coimts of red cells and haemoglobin. 

It is in suck cases that the estiniatiou of the dry residue of the blood seiiim 
would be of real valne could it be made short and simple enough for clinical 
work. Grawitz, who is the prophet of this branch of blood examination, 
gives an interesting case illustrating this point. 

A girl of twenty-live, suffering with peptic ulcer, and exceedingly pale, 
showed, on counting the corpuscles, 4,140,000 per cubic millimetre (no consid- 
erable reduction), and 90 per cent of haemoglobin. A second count showed 

iDeut. med. TVoch., 1889, No. 42. 



GASTRIC ULCER. 



317 



4,340,000 corpuscles aud 91 per ceut of lisemoglobin. But the dry residue 
of the serum was reduced to three-fourths its normal amount. The serum 
suffers in aniemia as much as the corpuscles do. Any influence which de- 
prived the serum of one-fourth of its normal solids (oedema being absent) 
nuist have really affected the corpuscles very much. Therefore the corpuscles 
nuist actually have been reduced to about 3,800,000, the reduction being 
masked by the concentration of the blood from vomiting. Lymph cannot 
iiave run into the vessels and diluted the serum, for (owing to the vomiting) 
the tide is all the other way. If then the serum is reduced to a quarter the 
corpuscles must be so likewise. Unfortunately, to test the dry residue of the 
blood serum requires more time, skill, and apparatus than clinicians are apt 
to have. It is valuable whenever we wish to know whether or not an anaemia 
is being masked by concentration of the blood. 

In severe cases the usual qualitative et'ldences of secondary anae- 
mia (deformities, scanty normoblasts) are to be found. 

Table XLII., A. — Gastkic Ujxek with IIemoiirhage. 













Per cent 




No. 


Age. 


Sex. 


Red cells. 


White 
cells. 


haemo- 
globin. 


Remarks. 


1 


32 




4,864,000 


22,000 


75 


Hemorrhage yesterday. 


2 


20 




3,968,000 


21,100 


45 


Chlorosis. 


3 


52 


F. 


2,031,000 


17,200 


30 


Hemorrhage and perforation. 


4 


27 




1,860,000 


15,300 


20 


Vomited small amount of blood. 


5 


23 




3,480,000 


15,000 


43 




6 


35 


M. 


1,640,000 


14,900 


18 


Bled four days ago. Diff. count 
500 cells: 
Polynuclear, 74 per cent. 
Lymphocytes, 25 " 
Eosinophiles, .4 " 
Myelocytes, .6 " 
Megaloblasts, 4 
Normoblasts, 1 

Reds stain well. 

Many polychromatophilic. 








2,104,000 


6,100 


24 


Sixth day. Diff. count 500 cells: 
Polynuclear, 60 per cent. 
Lymphocytes, 39 " 
Eosinophiles, 1 " 
Megaloblasts, 
Normoblasts, 1 








2,566,006 


7,000 


32 


Thirteenth day. Diff. count 500 
cells : 

Polynuclear, 58 per cent. 

Lymphocytes 39 " 

Eosinophiles, 3 " 
No nucleated reds. 








3,192,000 




40 


Twenty -first day. 






4,008,000 


" 6.606' 


55 


Thirty- second day. 


7 


29 


F. 


1,676,000 


14,750 


36 


Large hemorrhage. 


8 


55 


F. 


3,664,000 


14,800 


45 




9 


22 




4,820,000 


13,800 


50 


Perforation. 



318 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XLII. A. — Gastric Ulcer with Hemorrhage {Continued). 













Per cent 




No. 


Age. 


Sex. 


Red cells. 


White 


haemo- 


Remarks. 










cells. 


globin. 




10 


48 




1,448,000 


13,700 


10 


Five days after perforation. Diff. 
count 500 cells: 
Polyuuclear, 86 percent. 
Lymphocytes, 13.6 " 
Eosinophiles, .4 " 
Normoblasts, 1 


11 


42 


F. 


2,216,000 


13,500 


32 




12 


32 




3,256,000 


13,000 


35 


November 11th. 








2,564,000 




20 


November 14th. 
Pol3'nuclear. 83.2 per cent. 
S. lymphocytes, 10.4 
L. lymphocytes, 3.6 " 
Eosinophiles, 1.8 
Myelocytes, 1 

No nucleated reds; general tend- 
ency to small size, very few 








» 






large forms; moderate poiki- 
locytosis. 


13 


24 




5,016,000 


12,000 


52 




14 


29 




3,644,000 


11,400 


35 


Day after hemorrhage of iij. 


15 


72 




3,799,000 


10,700 


35 


Autopsy. 


16 


35 




3,024,000 


10,200 


55 


January 2d. 








3,392,000 


? 


55 


January 13th. 






3.712,000 




45 


February 5th. 


17 40 




3,868,000 


"9,966* 


50 




18 17 




5,000,000 


9,700 


45 




19 


27 




4,092,000 


9,300 


40 




20 


35 




1,364,000 
2,224,000 


17,200 
9,200 


20 
40 


No autopsy. 


21 


24 


F. 


3,076,000 


8,900 


15 


Bleeding. 


22 


20 


. . 


5,374,000 


8,650 


65 




23 


37 




3,267,000 


8,500 


30 


Hemorrhage six days ago. 


24 


45 




3,520,000 


8,400 


35 




25 


37 




4,188,000 


8,100 


35 


Bled one month ago. 


26 


30 


F. 


3,432,000 


7,820 


45 


Hemorrhage previous day. 








4,222,000 


10,600 


75 


Two weeks later. 








4,392,000 


6,700 


70 


Three weeks later. 


27 


44 




4,020,000 


7,600 


33 




28 


29 


. . 


5,000,000 


7,400 


50 


Slight hemorrhage. 


29 


26 




1,888,000 


7,400 


19 


Three days after hemorrhage: 

Poly nuclear, 57 per cent. 

Lymphocytes, 41 " 

Eosinophiles, 2 " 
No nucleated reds ; reds small but 

not much deformed. 


30 


22 




2,984,000 


7,200 




October 3d. 








3,436,000 


? 


21 


October 20th. 








3,612,000 


? 


34 


November 1st. 


31 


24 


F. 


1,892,000 


7,000 


30 


January 16th, after hemorrhage. 








2,304,000 


? 


27 


January 22d. 








3,064,000 


3,500 


35 


January 31st. 








3,920,000 


? 


48 


February 10th. 








4,680,000 


? 


55 


February 28th. 


'6)i 


20 




3,340,000 


7,600 


45 





GASTRIC ULCER. 319 

Table XLII. A.— Gastric Ulcer with Hemorrhage {Continued.) 



No. 


Age. 


Sex. 


Red ceiJs. 


White 
cells. 


Per cent 
hgemo- 
globin. 


Remarks. 


33 


52 




1,712,000 


7,000 


25 


Five days after hemorrhage. 
Diff . count 300 cells : 

PoJynuclear, 64 per cent. 

Lymphocytes, 35 " 

Eosinophiles, 1 " 

Normoblasts, 1. 


34 


33 




4,800,000 


7,000 


40 




35 


26 




3,280,000 


6,800 


30 




36 


24 




4,704,000 


6,500 


45 




37 


30 




2,544,000 


6,400 


30 




38 


13 




4,496,000 


6,300 


50 




39 


48 


F. 


4,900,000 


6,200 


40 




40 


23 


F. 


1,672,000 


6,000 


40 


One pint of blood vomited yester- 
day ; blood in stools ; recovery. 


41 


30 




3,920,000 


6,000 


30 


Bled seven days ago. 


42 


24 




3,196,000 


5,900 


15 




43 


26 


F. 


2,968,000 


5,300 


45 


Exclusive rectal feeding eight 
days. 


44 


19 




4,432,000 


5,000 


58 


Grippe and tonsillitis. 


45 


24 




4,625,000 


5,000 


45 




46 


50 


M. 


1,554,000 


4,800 


25 


Polynuclear, 74 per cent. 
Lymphocytes, 23. 
Eosinophiles, 2 
Normoblasts, 2. 


47 


46 


M. 


3,324,000 


4,800 


35 


Fell to 15 per cent after hemor- 
rhage. 


48 


29 




2,584,000 


4,500 


25 




49 


38 




3,616,000 


4,300 


35 


Eleven days after profuse hemor- 
rhage. 


50 


29 


F. 


1,972,000 


4,000 


38 


Recovery. 


51 


26 




4,312,000 


2,600 


45 





Gastric Ulcer with Hemorrhage. 



White Cells. 

Between 2,000 and 6,000 17 

6,000 " 8,000 23 

8,000 " 10,000 17 

" 10,000 " 12,000 6 

« 12,000 " 14,000 10 

" 14,000 " 16,000 7 

« 16,000 " 20,000 o 3 

" 20,000 " 24,000 3 

Total 86 



320 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XLII., B. — Gastric Ulcer without Hemorrhage. 



No. 


Age. 

27 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin.. 


Remarks. 


1 






22,000 


90 1 


October 31st. 










15,200 




No vein her 1st. 


2 


20 




5,716,000 


13,600 


85 1 




3 


20 






12,800 
6,800 
8,200 


60 
65 
65 


.March 14th : lead hi urine. 
March 20th. 
Aj^iil 2(1. 


4 


17 




5,380,000 


12.100 


60 




5 


22 




5,040,000 


12,000 


45 




6 


25 






11,900 
13,600 


80 
70 
80 


July 20th. 
July 30th. 
AuiTUSt 8th. 


7 


21 




5,000,000 


11,800 


70 




8 


39 


F. 





11,100 


68 




9 


51 


.... 




10,800 


70 




10 


24 





6,988,000 


10,700 


48 


Vomiting. 


11 


19 


F. 


5,856.000 


10.650 


90 




12 


22 






19,200 


85 




13 


40 


F. 


4, 400, 000 


9,000 


53 




14 


23 


F. 





9,300 


90 




15 


22 


F. 




8,300 


75 




16 


29 






8.100 


65 




17 


27 






7,000 


75 




18 


30 






6,800 


70 




19 


30 






6,800 
3,400 
3,500 


70 


Before test breakfast. 
After test breakfast. 


20 


30 


F. 




6,800 


70 




21 


25 






6,550 


85 




22 


35 







6,500 


50 
45 


April 27th. 
June 6th. 


23 


47 


F. 




6.300 


57 




24 


21 


. 




6,000 


90 




25 


38 


F. 




5,800 


60 




26 


19 


F. 




5,600 


68 




27 


20 


F. 




4,300 


57 




28 


26 


. . . . 


3,21*6,660 


4.200 


30 




29 


23 




4,680,000 




25 




30 


21 


F. 


5.100,000 




70 





Hcemoglohin. 

As a rule the color index is low. Only one examiuation iu the 
cases of the Massachusetts General Hospital series showed an in- 
creased amount of haemoglobin per corpuscle, and as this was not 
repeated or verified, it may have been a mistake. In most of the 
other examinations the color index was low. 

Yet Osterspey records 1,900,000 red cells with 31 per cent of 
haemoglobin (color index =: .81) ; 3,296,000 with 70-per-cent haemo- 
globin (color index = 1.09); 4,048,000 with 84-per-cent haemoglo- 
bin (color index = 1.05). Such cases are certainly rare. 



GASTRIC ULCER. 



321 



White Cells. 

Leucocytosis is practically never seen except after hemorrhage 
and during digestion. When patients who have been fed for some 
time by the rectum are first given food by the mouth, the digestion 
leucocytosis may be very great, as in a case of the above series, in 
which the cells increased from 4,000 to 15,5001 The presence of 
a leucocytosis, when the influence of bleeding and digestion is ex- 
cluded, is against the diagnosis of ulcer of the stomach. 

Table XLIII.— Duodenal Ulcer. 



I 

No. Age, 



Sex. \ Red oells. 



White 
cells. 



Per cent 
haemo- 
globlD. 



1 53 



31 



21 



1,472,000 



1,876,000 
2,148,000 
2,440,000 
3,196,000 
2,904,000 
2,744,000 
2,820,000 

3,440,000 
3,832.000 
3,885,000 
1,960,000 



1,764,000 
3,232,000 

3,104,000 
3,968,000 
3,520,000 

5,296,000 
1,448,000 



U 928, 000 



24,000 



6,600 



20 



19 
17 
21 
23 

m 

23 






5U 

39 




43 




45 




48 


24,000 


28 


10,500 


25 


24,000 


40 


17,200 


45 


8,000 


45 




48 




50 


15,800 


80 


14.800 


75 


9,700 




14,200 


. . 


18,300 




14,800 


. , 


7,800 


10 



September 3d. Diff. count 500 
cells: Polynuclear, 75 percent; 
small lymphocytes, 22.4; large 
lymphocytes, 1.2 ; eosinophiles, 
1,2; myelocytes, 0.2; one nor- 
moblast. 

September 10th, ■ 

September 18th. 

September 24th, 

October 1st, 

October 8th. 

October 16th. 

October 23d. 

October 30th. 

November 6th. 

November 24th, 

December 15th. 

•October 27. Diff. count: Poly- 
nuclear, 86 per cent ; small 
lymphocytes, 10; large lym- 
phocytes, 1.2; eosinophiles, 2 ; 
normoblasts, 1, 

October 31st. 

November 6th, 

November 8th. 

November 14th. 

November 22d. 

November 26th. 

July 11th, 

.July 16th, 

.July 23d. 

Julv 27th. 

July 29th. 

August 2d. Diff . count 200 cells : 
Polynuclear, 65.5 per cent; 
small lymphocj^tes, 25,5; large 
lymphocytes, 9; eosinophiles, 
; megaloblasts, 1 ; normo- 
blasts, 4. 



322 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XLIII. — Duodenal Ulcer {Continued). 











White 


Per cent 




No. 


Age. 


Sex. 


Red cells. 


cells. 


haemo- 
globin. 


Remarks. 














August 8th. Diff. count 200 














cells: Polynuclear, 70percent; 














small lymphocytes, 13; large 














lymphocytes, 16.5; eosino 














philes, 0.5; normoblasts, 4. 








1,976,000 




15 


August 14th. 








2,500,000 


13,866 


15 


August 20th. Diff count 200 
cells: Polynuclear. 72.5 jicr 
cent; small lymphocytes, 14; 
large lymphocytes, 13; eosiuo- 
philes,'5. 








2,476,000 


10.800 


25 


August 26th. 








2,840,000 


12,500 


25 


September 2d. 








2,746,000 


10,800 


25 


September 9th. 


4 


47 


M 


2,100,000 


12,000 

7,650 

11,600 

11,000 


35 


July 24tli, much coffee grounds. 
July 29th (five da3'S fasting). 
Four hours after meal. 
Constant feeding, July 30th. 








2,480,000 


6,000 


38 


August 8th. 








2,630,000 


6,500 


36 


August 21st, operation. 


5 


54 




2,016,000 


11,600 


45 


Death. 


6 


29 








10,800 


80 




7 


48 








9,200 


88 




8 


35 








7,900 


53 




9 


50 








7,800 


62 




10 


30 




. 


3,776,000 


Normal. 


50 




11 


38 






1,700,000 


Normal. 


67 




12 


47 




. 


2,584,000 


5,600 


35 


August 7th. 








996,000 


8,000 


15 


August 8th, death. 



These figures are given simply to show that the blood in duode- 
nal ulcer undergoes much the same changes as in gastric ulcer, and 
needs no further comment. 

ACUTE GASTRITIS AND DYSPEPSIA. 

Acute gastritis or gastro-enteric attacks (Hayem's " embarras 
gastrique^^) do not affect the red cells or hsemoglobin, but are very 
often accompanied by leucocytosis (see Tables XLIY., A and B). 

Table XLIV., A, — Acute Gasteo-Enteritis 



No. 


Age. 


Sex. 


Red ceUs. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 


2 

72 






19,700 
13,800 
19,400 
30,400 
20.200 


75 
66 


September 23d, temp. 102°. 
September 27th. 
Mav 22d, acute. 
:\Iav 26th. 
3Iav 27th 



ACUTE GASTRITIS AND DYSPEPSIA. 



323 



Table XLIV., A — Acute Gastro-Enteritis {Continued). 



No. 


Age. 


sex. 


3 


31 


M. 


4 


8 


F. 


5 


50 


F. 


6 


13 


F. 


7 


28 


M. 


8 


30 


F. 


9 


20 


M. 


10 


36 


F. 


11 


23 


F. 


12 






13 


17 


F. 


14 


29 


F. 


15 


70 


F. 


16 


37 


M. 


17 


28 


M. 


18 


23 


F. 


19 


57 


F. 


20 


23 


F. 


21 


32 


F. 



Red cells. 



White 


Per cent 


cells 


haemo- 




globin. 


12,800 




9,200 




18,000 




17,800 


50 


15,100 


70 


15,000 


85 


14,400 


^ 


12,800 




9,100 




14,200 


80 


12,000 


67 


11,600 


68 


11,600 


86 


11,500 




17,000 




8,000 




11,000 


70 


11,000 




10,000 


90 


9,200 


68 


6,900 


90 


6,400 


65 


6,000 




5,400 


95 


5,200 


50 



Remarks. 



7,000,000 
4,800,000 

5,184, boo 



4,860,000 
6,'244,000 

4,600,000 

4,'632,b00 
4,186,000 

3,'86d,00b 

5,'l44,bbb 



May 29tli. 
June 5th. 
Temp. 104^ 
Temp. 101°. 



Well next day. 



Well next day. 

September 17th, temp. 103°. 

September 18th. 

September 21st, temp, normal. 

Well in three days. . 



Well in two days. 
August 5th. 
August 5th, 8 p. M. 
August 6th. 

Temp. 101°. 

Temp. 102°. 
Temp. 101°. 
Temp. 100°. 



Where this is the case, it may help us to exchide typhoid fever^ 
which has no leucocytosis. Even a twenty-four hours' dyspeptic 
attack may increase the leucocytes notably, as in Cases 1 and 2 in 
Table XLIV,, A, and the presence of such an increase need not 
make us suspect anything behind the dyspepsia. It is probably to 
be classed as a toxic leucocytosis due to absorption of morbid prod- 
ucts from stomach or intestine. Fibrin may be increased during 
the period of leucocytosis. 

Table XLIV., B. — Dyspepsia and Gastritis. 











White 


Per cent 






Age. 


Sex. 


Red cells. 


cells. 


hgemo- 


Remarks. 


z 










globin. 




1 


24 


M. 


6,280,000 


22,700 

12,800 




Gastralgia; constipation; whole 

belly tender. 
Three days later ; well in a week. 


2 


22 







21,000 


90 


Nervous periodic vomiting. 


3 


27 


i^'. 


4,750,000 


14,000 


74 


At mealtime, 11,200; four hours 
later, 12,150. 


4 


26 


F. 


4,920,000 


11,000 


55 


Dyspepsia. 





23 


M. 




11,000 




Acute gastritis. 



324 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XLIV., B. — Dyspepsia and Gastritis {Continued). 











White 


Per cent 






Arc. 


Sex. 


Red cells. 


cells. 


hasmo- 


Reuiark>. 


^ 










globin. 




6 






5,016,000 


8,924 


86 




7 


37 


M. 




7,326 


77 


Chronic gastric catarrh. 


8 


30 


F. 


3,678,000 


7,000 


75 


Nervous chspepsia. 

f Before meal, November 1st, 


9 


41 


M. 


4,524,000 


6,000 


68 


I 6,000; November 2d, 6,300. 
j After meal, November 1st. 
I 6,800; November 2d, 7,400. 














10 


49 i F. 


4,200.000 


4,000 


80 


Chronic gastritis. 


11 


18 j F. 


5,016,000 


3,200 


45 


Dj'spepsia. 


12 


60 M. 


3.504,000 


2.800 


50 


Chronic gastritis. 



CHRONIC GASTRITIS. 

(See Cases 7, 10, and 12, Table XLIV., B.) 

Here the conditions are different and we never find an increase 
of the white cells, but often a decrease to malnutrition. Digestion 
may produce no leucocytosis, or the increase may be very slight and 
late in appearing (four to five hours after a meal instead of two to 
three hours). It was present in nine out of twelve cases in our 
series. 

Anaemia is very often present and may be extreme. It is be- 
lieved by very high authorities that a pernicious anaemia may be 
caused by chronic gastritis with atrophy of the gastric tubules. 
The writer has never had the good fortune to see such cases. 

The practical points about the blood of chronic gastritis are : 

(a) The not infrequently severe anaemia. 

(h) The not infrequent absence of digestion leucocytosis as in 
gastric cancer, from which therefore the absence of digestion leuco- 
cytosis does not distinguish it. 

The presence of a leucocytosis militates against the diagnosis of 
chronic gastric catarrh, and, if hemorrhage is excluded, points tow- 
ard cancer. 

HYPERACIDITY AND HYPERSECRETION. 

Lichty ^ found normal number of red cells and normal haemoglo- 
bin in hyperclilorhydria, 39 cases; hypochlorhydria, 63; achylia 
gastrica, 6; gastric dilatation, 11; chronic gastritis, 13; nervous 
dyspepsia, 14. 

1 Lichty: Phil. Med. Journ., 1899. p 326. 



DILATED STOMACH. 



325 



The leucocytes average higher in these conditions than in chronic 
gastritis or dyspepsia with normal or decreased secretions (see Table 
XLY.). Otherwise the blood is not remarkable. 

Table XLV. — Hyperacidity and Hypersecretion. 





Age. 


Sex. 


Red cells. 


White 


Per cent 
haemo- 


Remarks. 


z 










globin. 




1 


55 






14,000 


75 




2 


Adult. 


M. 


5,024,000 


12,300 


82 




3 


30 


F. 


5,768,000 


10,800 


82 


Chronic gastritis. 


4 


40 


M. 


5,300,000 


10.000 


85 


Slight digestion leucocytosis ; 
12,270 before meal, 14,300 three 
hours later. 


5 


31 






9,300 


80 
85 


November 3d. 
November 11th. 


61 58 






8,700 


72 




7 


40 


M. 


3,340,000 


7,780 


72 


Dilated stomach ; no digestion leu- 
cocytosis. 


8 


27 




4,348,000 


7,400 


60 


Anaemia. 


9 


37 






7,000 


70 




10 


60 






6,600 


85 




11 


28 


F 


4,016,000 


5,994 


76 




12^ 57 


M 


4,160,000 


3 600 


34 


Lead poisoning and dilated stomach 



Dilated Stomach 



30 






11,000 


70 


22 




6,216,000 


10,400 


83 


24 






9,900 


90 


29 






9,600 


78 


51 




4,184,000 


9,600 




47 




4,720,000 


8,000 




50 







6,400 


65 


30 




5,000,000 


6,000 




49 






5,800 


76 


43 






5,800 


85 


42 






4,800 


80 


64 




5,264,000 


4,600 


70 



Movable kidney 



Before test breakfast, 10,200. 
After test breakfast, 5,500. 

Tuberculous laryngitis. 
Before test breakfast, 8,600. 
After test breakfast, 12,400. 



DILATED STOMACH. 

In many cases proteid absorption is so faulty that the blood is 
severely starved, but the ancemia may be concealed by the concen- 
tration of the blood brought about by the constant vomiting of large 
amounts of fluid. Kussmaul has shown that patients often vomit 
more fluid than they ingest, and it is obvious what must be the drain 
of this process on the fluids of the blood and all other tissues. 



326 SPECIAL PATHOLOGY OF THE BLOOD. 

Digestion leucocytosis is often absent, as in cancer or chronic- 
gastritis. 

CORROSIVE GASTRITIS. 

The blood was examined in a case of this kind in 1895 at tlie 
Massachusetts General Hospital with the following result: lu^d 
cells, 3,792,000; white cells, 32,500; haemoglobin, 53 per cent. 

DISEASES OF THE IXTESTIXE. 
Influence of Saline C'athartics ox the Blood. 

Hay ' gives the following figures, showing the effect of sulphate 
of sodium in concentrating the blood : Healthy man of thirty-three, 
3:35 P.M. Eed corpuscles, 5,025,000; given 85 c.c. of a concen- 
trated solution of sulphate of sodium in water; thirty-five minutes 
later blood count showed red corpuscles, 6,540,000; sixty-five 
minutes later blood count showed red corpuscles, 6,790,000; four 
hours later blood count showed red corpuscles, 4,930,000. Evi- 
dently much fluid was drawn out of the blood-vessels, and then 
within four hours the tissues had sui)plied the loss and the blood 
had returned to its normal density. 

Hay also showed that dilute solutions of the same salt had far 
less effect in concentrating the blood. Further he demonstrated 
that if the blood is already concentrated when the saline is given, no 
purgative effect follows. 

Grawitz confirm-s these results; he found also that common salt 
still further concentrates the blood (hence its production of thirst), 
and considers that (as this concentration accelerates coagidatlon) 
the household use of salt water as a remedy to stop hemorrhage is 
well founded. 

ACUTE DYSENTERY. 

(Shiga's bacillus) (see page 539). 

ACUTE ENTERITIS. 

Practically the great majority of cases of acute enteritis are part 
of a gastro-enteric attack, and in Table XLIV. (see page 322) the 
two have been lumped together. What was said of that table ( p^ige 

Mlay; "The Action of Saline Cathartics." Journal of Anatomy and 
Physiology, 1882, p. 430. 



ACUTE ENTERITIS. 



327 



323) need not be here repeated. Besides the slight leucocytosis 
there mentioned, we may find in cases in which the stools are very 
watery a temporary concentration of the blood with increased sj^e- 
cific gravity and red corpuscles. In infants the lymphocytes are 
apt to be increased at the expense of all the other varieties.' Eosino- 
philes may be absent. Thus in a case of subacute colitis following 
an attack of influenza pneumonia, Wochnert found ninety-seven per 
cent of lymphocytes in a total count of 14,000 white cells. The 
other three per cent were polynuclear.^ 



Table XL VI. — Enteritis, Colitis, and Dysenteky. 



c. 


A^e. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hiemo- 


Remarks. 


-^ 








globln. 




1 


44 






23,100 

23,800 
29,100 
30,200 
16,700 
15,900 


90 


Jauuary 10th. Enteritis. 
January 18tli. 
January 19th. 
January 21st. 
January 23d. 
January 27th. 


2 


22 






19,400 

17,800 
25,400 
24,200 
21,000 
27,200 
14,600 


80 


September 15th Chronic entero- 
colitis. 
September 17th 
September 19tli. 
September 20tli. 
September 24th. 
September 27th 
October 10th. 


3 


45 


M. 


3,840,000 


17,000 
14,300 

7,700 
8,800 


50 


August 26th. Chronic dysentery. 
September 3d 

September 5th. Dysentery ceased. 
September 20th. 


4 


25 


F. 




17,000 




Chronic entero-colitis. 


5 


26 






14,800 
7,600 


50 


September 7th. Acute. 
September 9th. 


6 


Adult. 


M. 


3,624,000 


13,000 


58 


Chronic entero-colitis. 


7 


33 






12,600 


90 


Chronic. 


8 


Adult. 


ii. 


4326, boo 

2,732,000 

4,488,000 


12,400 

10,600 

6,000 




Ulcerative colitis. 
Two weeks later. 
Three weeks later much improved. 


9 


39 


F. 


6,776,000 


8,900 


166 


Acute febrile dysentery; bloody 
movements every hour. 


10 


3 


F. 


4,800,000 


7,900 




Ulcerative colitis. 


11 


40 







7,800 


30 




12 


Adult, 


M. 


4,100,000 


7,560 


72 


Chronic enteritis. 


13 


27 


M. 


4,872,000 


7,000 




Chronic diarrhoea and tetany. 


14 


20 


M. 


i 5,00^,000 


6,460 


39 


Chronic diarrhoea (tuberculous?). 



' But a summer diarrhoea without signs of colitis Zahorsky (N. Y. Mea 
Journ., 1903, vol. 78. p. 505) finds the polynuclears increased and the lymph- 
ocytes diminished in proportion to the severit}'- of the ease. 

* Journal of the American Medical x\ssociation, February 2d, 1901. 



3-2 


,8 




SPECIAL PATHOLOGY 


OF THE BLOOD. 




Table XL VI.— Enteritis, 


Colitis 


AND Dysentery {Continued). 










White 


Per cent 




. 


Age. 


Sex. 


Red cells. 


cells. 


hienio- 


Remarks. 


2: 










globln. 




15 


31 




2,198.000 

2,224,000 
2,484,000 
2,230,000 
1,976,000 


5,800 
...... 


45 

37 
34 
40 
42 


February 14th. Clirouic troijical. 
Severe secondary anaemia. 

February 18th. 

February 25th. 

March 4th. Diff. count, 200 c ells. 
Folynuclear, 49 per cent ; lympho- 
cytes, 33; eosinophiles, 17; mye- 
locyte, 1; normoblasts, 2; meEralo- 
blast, L 


16 


29 






5,600 


90 




17 


26 


M. 


4,900,000 


5,300 


80 


Bloody stools ten days. 


18 


65 


M. 




5,200 


80 


Catarrhal entero-colitis. 


19 


40 


F. 


2,996,000 


5,000 


37 


Chronic colitis. 


20 


27 


F. 


4,500,000 


5,000 


70 


Diarrhoea. 


21 


34 


F. 


3,920,000 


5.000 


70 


Chronic colitis. 


22 


45 






3 600 


80 





CHRONIC DIARRHOEA. 

(See Table XLVI) 

In acute diarrhoea the other tissues respond to meet the loss of 
fluid sustained by the blood, and the blood is soon normal again. 
But when this process goes on long, the body becomes so wasted 
that the blood must share in the starvation and the albuminoids are 
drained out of it, leaving it watery and i^oor in corpuscles. A pa- 
tient of Grawitz after years of chronic dysentery had but 1,880,000 
red cells per cubic millimetre, while the serum had twice the nor- 
mal amount of water and half the normal amount of solids. I 
have seen the count fall as low as 1,928,000 in a case of prolonged 
colitis, with final recoveiy. In another case the red cells reached 
no lower than 2,440,000, but the hsemoglobin was only ten per cent. 
A differential count of this man's blood showed the following: 

Per cent. 

Polymorphonuclear neutrophiles 66.3 

Lymphocytes (small) 24.9 

Lymphocytes (large) 6.0 

Eosinophiles , 1.4 

Myelocytes. 1.4 

While counting 400 leucocj^tes I saw 8 normoblasts and 5 megalo- 
blasts. The total leucocyte count was 9,800 per cubic millimetre. 
Cases 8, 15, and 19 of the series in Table XLVI showed simi- 



INTESTINAL OBSTRUCTION. 



329 



lar conditions. The haemoglobin, however^ usually suffers most, 
and the color index is low. 

Leucocytosis is rare, but does occasionally occur, possibly owing 
to some complication or auto-intoxication. 



Table XL VII. — Intestinal Obstruction. 



^ 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hgemo- 
globin. 


Remarks. 


1 


1 rao. 






34,200 




Intussusception, died. 


2 


.... 






22,100 
21,700 


• • 


Twenty -first day, strangulated 

hernia. 
Twenty-second day, autopsy. 


3 






3,120,000 


20,800 




Cancer. 


4 


'52' 


M. 


5,568,000 


18,860 
18,800 




May 6tb, cancer. 
May 17th, cancer. 


5 


65 







15,400 


85 




6 


Adult. 


M. 




14,666 




No faeces three days. 
No urine two days. 






















12,400 


•• 


One day later, no fseceS; urine 
drawn by catheter. 










4,100 




Three days later, bowels moved six 
times. 


7 


47 






13,300 


75 




8 


50 
35 


F. 
M. 




12.200 
12,000 




Cancer of uterus. 


9 


3,504,600 


Chronic obstruction with hemor- 
rhage. 
Obstruction (by a band). 


10 


21 


M. 


5,150,000 


12,000 




11 


56 


F. 


4,440,000 


12,000 


52 


Cancer. 


12 


57 


F. 


4,272,000 


11,000 


75 


Cancer. 


13 


Adult. 


M. 


5,800,000 


6,800 






14 


45 






6,600 


60 


Double ovarian cyst. 


15 


72 


M. 


4,850,666 


6,000 






16 


29 


. . 




6,000 




Obstruction by band : operated. 


17 


58 




4, 480", 666 


5,800 


96 


Cancer. 


18 


Adult. 


M. 


5,200,000 


4,000 






19 


Adult. 


M. 


5,540,000 


4,000 







Cholera is discussed on page 231. 

For Appendicitis see Abscess, page 245. 

INTESTINAL OBSTRLCTION. 

Gushing ^ in 1898 first noted the leucocytosis (presumably toxse- 
mic) associated with intestinal obstruction. 

Bloodgood's ^ conclusions are as follows : 

Within a few hours of the occurrence of obstruction the leuco- 
cytes rise rapidly. If obstruction is partial the counts are between 

Hopkins Bull., November, 1898. 
Prosi'. Med., December, 1901. 



^ Cushing: J. 
^ Bloodgood : 



330 



SPECIAL PATHOLOGV OF THE BLOOD. 



14,000 and 16,000; if complete usually 20,000 or more. The higher 
the count and the shorter the duration the greater the probability of 
gangrene. If there is a count of over 20,000 within the first twenty- 
four hours, the chances are that gangrene is present. On the second 
day the counts do not change much. Then if gangrene or peritonitis 
occurs the count begins to fall, otherwise tlie count remains high until 
the fourth or fifth day, when the leucocytes gradually fall whatever 
the condition of the abdomen. If after three days of obstruction the 
count is still over 20,000, the prognosis is good. If the count is be- 
low 15,000, the probability is that gangrene, peritonitis, or fatal 
autointoxication has occurred, Bloodgood thinks the leucocyte count 
of great value on post-operative complication suggesting obstruction 

DISEASES OF THE LIVER. 



CATARRHAL JAUNDICE. 

The serum is colored yellow or greenish-yellow and contains bile 
pigments in solution. It has been asserted that jaundice can be 
recognized here before it shows in the skin or urine. In mild cases, 
i.e., when some bile goes to the intestine and the obstruction is not 
of long standing, the Mood is j^i'ttcticaUi/ normal, as the cases in 
Table XL VIII. show. Achard and Loeper ' studied twenty-four 
cases of jaundice of various origins and found in the catarrhal 
type at the beginning a slight pol3'nuclear leucocytosis; at the 
end a low jjercentage of polynuclears with slight eosinophilia. 

Table XLVIIL— Catarrhal Jauxdice. 











Per cent 




Age. 


Sex. 


Red cells. 


White cells. 


liseino- 
globln. 


Remarks. 


47 




14,700 




Seven weeks. Catarrhal (?). 


25 






11,100 


85 




21 


M. 




10,500 


81 




26 






10,400 


60 




44 


M. 




10,200 






41 


. . 




10,000 


62 




25 


h\ 


4,310,000 


10,000 

10,000 

8,000 


77 
90 




80 


F. 




9,600 


68 




84 






9,200 






42 


ivi. 


2,896V000 


8,775 


47 


Alcoholic gastritis. 


40 






8.200 
8,100 


75 





^ Achard and Loeper: Soc. de Biol., 1901, p. 217. 



DISEASES OF THE LIVER. 



331 



Table XLVIII. — Catarrhal Jalts'dice {Gonti aued). 











Per ceut 






Age. 


Sex. 


Red cells. 


White cells. 


ha?mo- 
globin. 


Remarks. 




40 






8.000 








28 






8.000 








87 






7.500 








80 






7.500 








26 


M, 




7,500 








21 


M. 


4,800,000 


7,500 


65 






44 







7,500 


70 






80 


M. 




7.400 


64 






80 


M. 




7.800 








48 




3,036,000 


7.000 
7.240 


45 


August 13th. 
August 14th. 




53 


M, 


4,240,000 


6.798 


79 






24 







6,800 








44 






6.200 




Obstruction. 




29 


M. 




6.200 


82 








M. 


4,996,000 


6,000 


78 






24 






6,000 


78 






23 






5.500 


90 






25 


' ' 




5,400 


30 


Polynuclears, 78 per cent; 
cytes, 19; eosinophiles, 1 
cytes, 0.75; 1.25 (?); reds 
formed; 1 normoblast. 


lympho- 
; myelo- 
pale, de- 


24 






5.400 


90 






32 


•• 




5,'60(),00{) 


5,300 
4.700 


75 


March 16th. 




35 


M. 


4,350,000 


4.900 


85 






44 




3,168,000 


4.800 


85 






29 


F. 




4.200 
9,600 


85 






19 


h\ 




4,000 









Only one of these cases shows any leueoeytosis, and the red cells 
and hsemogiobin have not suffered except in the alcoholic case 
in which other causes for anaemia were present. This is contrary 
to the observations of Grawitz, who constantly found, leucocytosis, 
but agrees with those of v. Limbeck and Hayem, w4io never found 
any increase of leucocytes or any other changes in the blood count. 
Coagulation in this or any other type of obstructive jaundice may 
be very slow, but this is especially apt to be true in gall-stone cases 
even if no jaundice is present. Coagulation may be increased to 
eleven minutes (Osier) and patients may bleed to death during 
operation on gall stones. The amount of fibrin is normal. Von 
Limbeck noticed an increased resistance of the red cells to the influ- 
ence of distilled water and dilute saline solutions which in normal 
blood dissolve the haemoglobin. He asserted also that the size of 
the red corpuscles was greater than normal, their volume in a given 



332 SPECIAL PATHOLOGY OF THE BLOOD. 

amount of blood being seventy-seveu to eighty-one per cent (i.e., 
they take up seventy-seven to eighty- one per cent of the room occu- 
pied by the drop), while the normal is about forty-four per cent.' 

Qualitative Charif/t^s. 

Grawitz noted in severe cases that crenation took place much 
more rapidly than usual in freshly drawn blood, and that the rou- 
leaux formation did not take place. This latter point was also 
noticed by Hofmeier ^ in icterus of the new-born. Silbermann ^ no- 
ticed in the same disease great deformities in the size and shape of 
the cells. In severe febrile icterus Weintraud noted in the red 
cells the white spots and streaks witli active (molecular) movements 
described by Maragliano (see page 79) as endoglobular degenerative 
changes. 

Summary. 

Occasionally there is slight leucocytosis at the onset, otherwise 
normal blood, with some degenerative changes in severe cases. 

Diagnostic Vahie. 

The constant presence of leucocytosis excludes an uncomplicated 
"catarrhal" jaundice, and points to the probability of malignant 
disease or inflammation (cholangitis, abscess). Syphilis and cir- 
rhosis of the liver might show the same condition of the blood. 
From a severe cholaemia the absence of any marked anaemia and 
leucocytosis distinguishes a purely catarrhal case. (For the changes 
in cholaemia see page 339.) 

CIRRHOSIS OF THE LIVER. 

1. Ordinary (Atrophic) Cirrhosis Without Jaundice. 

In the early stages (according to Hayem) neither the red cells 
nor the haemoglobin fall considerably. Most other observers (per- 
haps thinking chiefly of the later stages) report marked anaemia. 
In Da Costa's 18 cases the red cells averaged 3,404,000 and the 
haemoglobin 47 per cent. Wlajew' counted from 3,000,000 to 

^ Capps (Journ. Med. Research, December, 1903) finds no such change. 

2 "Die Gelbsucht der Neugeborenen," Stuttgart, 1882. 

3 "Die Gelbsucht der Neugeborenen. " Arch. f. Kinderheilk, , 1887, p. 401. 
4Ref. in Petersburger med. Woch., 1894, No. 43. 



CIRRHOSIS OF THE LIVER. 



333 



4,000,000 red cells. The count may be increased, after a tapping in 
cases with ascites, owing to the concentration of the blood from the 
rapid refilling of the belly with serum. Grawitz, on the other hand, 
noticed precisely the opposite effect in a patient whose blood before 
tajDping had been concentrated by cyanosis, the heart's action being 
embarrassed by the ascites. After tapping, when the heart's action 
had become easier and stronger, the cyanosis disappeared and the 
blood count fell from 4,700,000 to 4,300,000. In v. Limbeck's 
case it rose from 4,680,000 to 5,160,000. The moral is that we 
should draw no inferences from the count of red cells soon after a 
tapping. 

The forty-three cases in Table XLIX. , A, , were all advanced 
and their red cells averaged only 3,580,000 -\- per cubic millimetre- 
They steadily decrease as the disease progresses, one case getting 
as low as 1,300,000; but the anaemia may be concealed by cyanosis 
and concentration. 

Qualitative Changes. 

Hayem noticed spontaneous agglutination of the erythrocytes, a 
great tendency to adhere to each other. Von Limbeck looked for 
it, but could never find it. Hayem and Maragliano noticed degen_ 
erative endoglobular changes in the red cells (^' eta.t crihriforme^^). 

Tarle XLIX., A. — Cirrhotic Liver wiTHorT Jauis^dice. 



1 

1 




White 


Per cent 




^•1 Age. Sex. 


Red cells. 


cells. 


haemo- 


Remarks. 


z ' 






globin. 




1 58 ; .. 


4,504,000 


29,300 


60 


Temp. 100^ Delirium tremens. 




1 




18,500 




Fourth day. 


2 


35 .. 


908,000 


26,000 


20 


Intestinal liemorrliage. Diff. count 














500 cells: Polynuclear, 85 per 














cent; lymphocytes, 14; eosino- 














philes, 0.8; myelocytes, 0.2; nor- 














moblasts, 10: megaloblasts, 0. 








1,732,000 


19,800 


25 


Seventh day. DifCr count 500 cehs: 
Polynuclear, 88 per cent; lym- 
phocytes, 10 ; eosinophiles, 1 ; 
myelocytes, 1 ; normoblasts, 2. 








2,456,000 


16,900 


23 


Fourteenth da v. 








3,098,000 


14,000 


35 


Thirtieth day.' 


3 


53 






23,400 
5,800 


•• 


First day. Uraemic symptoms. 
Eleventh day. Autopsy. 


4 


34 




4,000,000 


18,900 
8,400 


58 


December 21st. 
December 23d. 
December 24th. 


5 


51 






is", 200 


30 


Haemoptysis. Autopsy. 


6 


53 


F. 


2.950,000 


16,000 




Recent hemorrhage. 



334 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XLIX., A. — Cirrhotic Liver without Jaundice {Contihv.ecJ). 











White 


Per cent 




o 


Age. 


Sex. 


Red cells. 


cells. 


haemo- 


Remarks. 


z; 










globin. 




7 


54 






14.000 




Tapped ; 328 ounces. 


8 


63 




3,'ooo,oob 


13,000 


55 


With mitral disease. 


9 


41 


M. 


4,300,000 


12,700 


55 


Liver enlarged. Ascites. 


10 


60 






11,800 






11 


47 






11,600 


60 


Autopsy. 


12 


40 




4,896,000 


11,500 


50 




13 


46 






10,500 


60 




14 


63 






10,000 






15 


48 




4,052,000 


9,800 


55 




16 


48 


M. 


4.992,000 


9,000 


62 


Recent hemorrhage. 


17 


53 


M. 


2,120,000 


9,000 


23 


March 15th. 








1,300,000 


7,500 


22 
15 
15 


April 8th. 
April 18th. 
April 29th. 








2,350,000 


6,000 


20 


Mav 10th. 








2,375,000 


5,300 


26 


May 12th. 








2,450,000 


5,200 


20 


June 10th. 








4,500,000 


7,800 


25 


June 16th. 


18 


56 






9,000 


62 


Hypertrophy. 


19 


50 


. 


3,'i6o,oob 


8,400 


45 




20 


50 


M. 


3,440,000 


8,320 


46 


Liver enlarged. 


21 


34 


M. 




7.900 


95 




22 


49 






7,800 


. . 


Tapped : 144 ounces. 


23 


38 




5,360,000 


7,600 


55 




24 


56 


ii. 




7,500 


68 




25 


47 






7,500 


70 




26 


64 






6.400 


85 




27 


57 




3*744,000 


6.400 


58 




28 


43 




2,620,000 


6,200 


35 




29 


53 






6,200 


60 




30 


48 




4,888,000 


6,100 


65 




31 


38 


F. 




5,700 


65 










5,'720,00b 


5.200 


46 


Differential normal count. 


32 


45 




2,830,000 


5,500 


40 




33 


14 




3,480,000 


5,500 


55 




34 


54 


M. 





5,400 


64 




35 


46 






5,200 


80 




36 


56 


M. 


4,680,000 


5,000 


48 


Liver atrophic. July 12th. 








4,312,000 


4,000 


62 


July 25th. 


37 


42 


M. 


2,920,000 


4,500 
13,400 
15,300 


56 


October 30th. 

Xovember 7th, during digestion. 

November 11th, during digestion. 


38 


53 


M. 




3,800 


72 




39 


54 


F. 




3.300 


65 




40 


63 


M. 


3,*844,00b 


3,000 






41 


45 






2,600 


80 




42 


50 


M. 


3,*568,bbb 


2,400 


50 




43 


52 


M. 


3,440,000 


2,400 


50 





HcBmoglohin. 
Usually the color index is low; the average was 0.66 in the ten 
Massachusetts General Hospital cases. 



CIRRHOSIS OF THE LIVER. 



335 



White Cells. 

Except during severe nervous manifestations of toxaemia and 
after recent hemorrhage none of our cases showed any leucocytosis 
and the average count was 7,240, some cases having notably low 
figures (2,400, 3,000, 4,500). 

Hayem's and Da Costa's results agree with mine. Von Lim- 
beck makes no definite statement. Eosenstein and Wlajew found 
leucocytosis, the latter 12,000 to 17,000. Possibly their cases in- 
clude the forms of cirrhosis with jaundice in which (see Table 
XLIX., B) the white cells are more often increased. 

The forms of hypertrophic cirrhosis ivithout jaundice are here 
classed with the atrophic cases whose blood has just been described. 



Table XLIX., B. — Cirrhotic Liver with Jaundice. 











White 


Per cent 




c 


Age. 


Sex. 


Red cells. 


cells. 


hsemo- 


Remarks. 


^ 










globln. 




1 


54 






36,400 


85 


Death. 


2 


29 




3,'700,00b 


20,000 


30 


Toxic symptoms. Delirious. 


3 


42 


M. 


1,024,000 


19,600 


36 


Autopsy. 


4 


38 


M. 


3,400,000 


19,500 


50 




5 


32 




2,392,000 


19,300 


55 


Syphihs. 


6 


51 




3,960,000 


19,200 


47 


Haemoptysis. Delirious. Death. 


7 
8 
9 


32 
36 

45 


•• 




18,200 
15,600 
14,000 


65 


Temp. 102°-104°. Liver enlarged. 


ii. 




65 


Liver enlarged. 


10 


49 


• • 


4,*228/obb 


13,000 
34,500 


55 


July 14th. 

July 23d. Autopsy. 


11 


28 






12,400 


65 


Ascites. 


12 


57 






12,200 


63 




13 


35 




5,016,000 


12,000 




Liver enlarged. 


14 


29 






11,600 


85 




15 


57 






10,500 


85 


Atrophic. 


16 


43 






10,000 


78 




17 


54 







9,300 




Ascites. 


18 


58 




2,'640,b00 


8,800 






19 


33 




3,740,000 


8,700 

19,200 
22,000 


50 


Differential count, 400 cells: Poly- 
nuclear, 87 per cent; lympho- 
cytes, 12; eosinophiles, 1; normo- 
blast, 1. 

Twentieth day. High fever, toxic 
symptoms. 

Twenty-fourth day. High fever, 
Toxic symptoms. Autopsy. 


20 


49 






8,600 


85 




21 


52 






8,600 


70 




22 


65 






8,100 


75 


Hypertrophic. 


23 


65 







7,800 


80 




24 


65 







6,300 


64 


Hypertrophic. 


25 


34 




3,868,000 


5,250 


58 





336 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XLIX., B.— CmRnoxic Liter avith Jaundice {Continued) 



6 
2; 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
baemo- 
globin. 


Remarks. 


26 

27 
28 
29 


30 

36 
50 

57 


M. 
F. 


3,872,000 
3,640,000 
3,944,000 
2,064,000 
2,904,000 


4,600 

■ 4,300 
2,400 


60 
62 
63 
50 
54 


April 29th. 
May 6tli. 
June 13tli. 

Jaundice only transient. 
Autopsy (hypertrophic cirrhosis). 
Polynuclear cells, 83 per cent ; lyin 
phocytes, 17;?. 



2. Haxot's Cirrhosis. 



Bed Cells. 



True (biliary) hypertrophic cirrhosis tvith jaundice has, according 
to Hayem, an intense anaemia in many cases. In others it has no 
more effect on the blood than ordinary atrophic cirrhosis. I have 
never met with a case. 

Hannoglohin. 

In a single case of this variety of cirrhosis Ha3'em found in four 
successive blood examinations a color index of more than 1. His 
counts are as follows : 



Date. 


Red cells. White cells. ^ Per:cent 
haemoglobin. 


Color index. 


January 9tli 


1,599,600 

1,884,000 1 21,803 
1,798,000 18,082 
1,971,000 15,500 


41 
50 
50 
53 


1.27 


January 11th 


1.39 


January 12th 


1 46 


January 15th 


1.40 







Dried specimens showed an increased average diameter of the 
cells as in pernicious anaemia. The patient died January loth, 
and the autopsy confirmed the diagnosis of hypertrophic cirrhosis. 

Only one of our cases of hypertrophic cirrhosis with jaundice 
showed this condition — Case 27 in Table XLIX., B. The corpus- 
cles numbered 2,064,000, or 40 per cent, and the haemoglobin 
50 per cent, a color index of 1.25. This case was jaundiced at the 
time of the examination. 

I have seen no confirmation of Hayem' s observations by any other 
writer. 



HYDATID CYST OF THE LIVER. 337 

White Cells. 
In Hanot's cirrhosis leucocytosis is apparently commoner than 
in the other varieties. Hanot and Mennier found from 9,000 to 21,- 
800 leucocytes per cubic millimetre in five cases, and an average of 
6,()00 in ordinary cirrhosis. Among the 29 jaundiced cases of cir- 
rhosis in my series, 14 (about fifty per cent) showed leucocytosis, 
due, I conjecture, to the relatively late toxaemic stage in which most 
of these cases were at the time the blood was taken. The toxaemia 
of fibrous hepatitis, like that of fibrous nephritis, is probably capa- 
ble of producing leucocytosis. Similarly high counts were found 
in some of the non- jaundiced cases while in the toxeemic state. 

Diagnostic Value. 
The blood of either form of cirrhosis has no diagnostic value, so 
far as I know, except to exclude abscess and hydatids. If no leuco- 
cj^tosis is present, abscess and hydatid cyst can usually be excluded .- 

HYDATID CYST OF THE LIVER. 

The earlier observations which I have met with are those of 
Hay em and Neusser. Hayem states that the blood shows leucocy- 
tosis and increased fibrin. Neusser considers that the increase of 
eosinopliiles which he finds in hydatids serves to distinguish them 
from hydronephrosis, dilated gall bladder, etc. Neusser's discovery 
of eosinophilia in hydatid disease has been abundantly' confirmed of 
late. Memmi ' in 12 cases found 10 to 18 per cent of eosinophiles; 
Darguin and Tribondeau ^ add one similar case, and others are men- 
tioned by Achard and Clerc ^ (up to 40 per cent of eosinophiles) 
by Laubry * (10 per cent), and by Abbe " (4 per cent). Tuf&er and 
Milian ® give brief notes of 5 cases with 4 to 8 per cent of eosono- 
philes out of 10,000 to 15,000 leucocytes. Lepine ' in hydatid of the 
liver counted 28,000 leucocytes with 18 per cent eosinophiles (4,500 
absolutely) . 

Seligman and Dudgeon' report the following observations in 
hydatid of the liver : 

^ Memmi: Kef. in La Sem. Med., November 13tb, 1901. 

- Darguin and Tribondeau : Presse Med., November Gth, 1901. 

3 Acliard and Clerc; Ref. in Arch. Gen. de Med., 1902, p. 743. 

'* Laubry: Ibidem. =Abbe: Ibidem. 

^Tuffier and MiHan: Soc. de Cbirurg., February 2oth. 1902 

'Lepine: Soc. de Biol., March 8th, 1902. 

» Seligman and Dudireon: Lancet. June 21st, 1902. 

22 



338 



SPECIAL PATHOLOGY OF THE BLOOD. 



Date. 



1901— 
Dec. 27tli. 

1902— 
Jan. 13th. 



Feb. 20th . . 
March 13th. 
April 3d. . . . 



Red cells. 



6,290,000 



2,934,000 



3^ 5.S ■ ^ 2 



17,000 70 
7.000 

7,000 



57.0 

12.0 

1.0 

3.2 

LO 



m 


lit 


22.0 


20.0 


59.0 


28.0 


60.0 


29.0 


73.2 


22.2 


64.5 


34.5 



9 g 
it 



1.0 
1.0 



Remarks. 



Before operation. 



Three days after 

i draining cyst. 
1.0 Free purulent 

! discharge. 
1.4 More cysts evac 

I uated. 




Longridge ' reports a similar case with the following figures: 
Red cells, 4,400,000; white cells, 7,300: haemoglobin, 84. Differ- 
ential count: Polynuclear, 63.4; lymphocytes, 23 6; large myelo- 
cytes, 8.2; eosinophiles, 5.8 per cent. 

In a second case with suppuration in the cyst the leucocytes 
were 18,000 with 1.4 per cent of eosinophiles (252 absolute). 

Sabrazes " in 7 cases found always an increase in the eosinophile 
cells, sometimes slight and sometimes considerable; in tissues in 
the neighborhood of the cysts there was always a great accumulation 
of the eosinophile cells. It therefore appears that the echinococci 
have a positive chemotaxis toward the eosinophile cells. Polycyto- 
sis, polychromatosis, nucleated reds, or red cells with basophilic 
granules were not observed. Unually there was a leuocytosis, 
although sometimes it was not present. 

From these records of over thirty cases it appears that eosino- 
philia is the rule in hydatid disease icithout siqjjmration. Only 
two negative cases are so far on record (Bezancon and Weil ' and 
Gourand.* In three cases I recorded the following: 

EcHiNococcus Cyst. 



No. 


..e. 


Red cells. 


White cells. 


Per cent haemoglobin. 


Remarks. 


1 
2 
3 


31 


3,664,000 


8.650 
11,000 
34,000 


48 
95 


Iceland 



'Longridge; Brit. Med. Jour., November 8th, 1901. 
^Sabrazes: Munch, med. Woch., March 31st, 1903. 
3 Bezancon and Weil: Arch. Gen. de Med., 1902, p. 743. 
''Gourand; Soc. Anatom., January 10th. 1900. 



TOXEMIA IN HEPATIC DISEASE (" CHOL^MIA '"). 339 



ACUTE YELLOW ATROPHY OF THE LIVER 

Grawitz records a case with 5,150,000 red cells and 16,000 
white cells. 

A single case with autopsy was studied at the Massachusetts 
General Hospital in 1894, the blood showing 5,520,000 red cells, 
12,000 white cells, and 60 per cent of haemoglobin. 

Ewing reports three cases with leucocytosis, 15,000 to 21,000. 
•' The absence of rouleaux and early crenation mentioned by GraAvitz 
were not noted." 

PHOSPHORUS POISONING. 

Taussig,^ V. Jaksch,-^ Badt,^ and v. Limbeck* note an increase 
in the normal number of red cells per cubic millimetre. Taussig 
found 8,650,000 per cubic millimetre; Badt, 6,400,000, 6,500,000, 
and 6,800,000 in three successive cases; v. Limbeck, 6,500,000 and 
7,900,000. That this increase is not due to concentration of the 
blood through vomiting of liquid is proved by v. Limbeck's last 
case, in which no vomiting whatever took place. 

The count usually falls to normal within a few days. All these 
changes were verified in thirty-three cases at the Stockholm Hos- 
pital in 1892 (see Stockholm reports for 1892). 

The white cells in v. Limbeck's second case were increased to 
12,500. In V. Jaksch's live cases the counts were 58,750, 48,000, 
8,000, 4,070, and 3,400. 

TOXAEMIA IN HEPATIC DISEASE ("CHOL^MIA"). 

When jaundice is intense and of long standing, as in complete 
obstruction of the bile ducts by gall stones or tumors, the blood is 
weakened very notably, and haemoglobin and the count of corpus- 
cles fall steadily. Very little is to be learned upon the subject 
from the literature, but the qualitative changes mentioned under 
catarrhal jaundice are much more marked, and leucocytosis is apt 
to be present. I have studied the blood in one case of fatal chronic 
jaundice without fever and for which at autopsy no cause was 
found. The leucocytes ranged between 12,000 and 14,000. 

^ Arch, f, experiment. Path, und Pharm., vol. xxx. 

2Deut. med. Woch., 1893, p. 10. 

3 Dissert., Berlin, 1891. ■> Loc. cit., p. 34. 



340 



SPECIAL PATHOLOGY OF THE BLOOD. 



GALL STONES. 

Netter ^ and Sittmann ^ found p3'ogenic organisms in cultures 
from the blood of patients with gall stones, as have Gilbert and 
Girode^ and others. The slotv coagulation is of great surgical im- 
portance. Da Costa in 38 cases found that " gall stone does not 
of itself excite leucocytosis "; acute inflammatory complications 
raised the count in about one-third of his cases. Tlie maximum in 
28 cases was 18,800, the average 10,100. 

Of the 50 cases of this disease examined at the Massachusetts 
General Hospital 2 were complicated with cholangitis (see Table 
L., A), Excluding these 2, marked leucocytosis was present in 
only 5 of 50 cases. The red cells were low in 2 cases (2,800,000 
and 3,900,000). 

The absence of leucocytosis helps us to distinguish the disease 
from peritonitis and appendicitis, and to exclude suppurative clio- 
langitis. 

Table L., A. — Gall Stones. 



6 


Age. 


Sex. 


^ 






1 


25 




2 


39 


F. 


3 


34 


•• 


4 


30 


F. 


5 


63 


F. 


6 


29 


M. 


7 


60 


•■ 


8 


40 


F. 


9 


60 


F. 


10 


24 




11 


25 






12 


46 






13 


63 






14 


39 






15 


37 






16 


40 


] 


vr. 


17i 60 






18 


55 







Red cells. 



4,768,000 



4,820,000 
4,610,000 



4,520,000 

4,'i76Vobb 

4,'l68,00b 
4,'336,bob 



White 


Per cent 


cells. 


haemo- 




globin. 


28,200 




24.000 




24,000 


80 


26,400 




22.000 




20,000 




18,800 




16.200 




13.200 




10,000 




14.300 




20,700 




15,000 




13.000 




12,500 


72 


11,500 


70 


12,000 


80 


11,600 




11,400 


45 


11,300 




10,500 


65 


10,300 




10.250 




10,200 


45 


10,200 





Cholangitis also. 

Mav 7th. Hvdrops of gall bladder. 

MaV 8th. 

May 10th. 

Cholangitis. Autopsy. 

December 16th. 

December 18th. 

December 21st. 

First da}'. Pus in gall bladder. 

Fourth day. 

Fifth day. Operation. 

Temp. 100.5. 

Hj'drops of gall bladder. 



Obstructive jaundice. 
No pain. 
In colic. 



In pain. 



1 Progres Medical, 1886, No. 46. 

^Deut. Arch. f. klin. Med., 1894, p. 323. 

3 La Semaine Med.. 1890, No. 58. 



GALL STONES. 



341 



Table L., A. — Gall Stones {Continued). 





A^e. 


Sex. 


t?; 






19 


60 




20 


49 


F. 


21 


40 




22 


47 




23 


56 




24 


41 




25 


32 




26 


33 




27 


32 




28 


45 


F. 


29 


38 


F. 


30 


25 


F. 


31 


40 




32 


46 




33 


27 




34 


22 


M. 


35 


25 


F. 


36 


54 




37 


50 




38 


37 


. 


39 

40 

41 


54 

40 

48 


F. 


42 


29 


F. 


43 


57 


F. 


44 


37 


F. 


45 


48 




46 


58 


M. 


47 


57 


F. 


48 


51 


F. 


49 


28 




50 


24 


M. 



Red cells. 



White 
cells. 



Per cent 
haemo- 
globin. 



Remarks. 



4,448,000 



5.072,000 



3,288,000 
4,900,000 



4,336,000 
3,636,000 
2,'844,"obb 



4,320,000 



10,000 
10,200 
10,000 
9,900 
9,800 
9,700 
9,400 
9,400 
9,400 
5,200 
9,200 
9,200 
8,900 
8,800 
8,300 
8,200 
8,200 
8,000 
8,000 
7,800 
7,700 
7,600 
7,600 
7,400 
3,700 
11,500 
15,100 
10,600 
7,400 
7,400 
7,400 
7,300 
8,200 
6,700 
6,000 
5,400 
5,300 
5,200 
4,000 



58 Sixth day. Operation. 
90 Hydrops of gall bladder. 
90 Jaundice. 



85 
90 



100 
60 



60 
80 
60 

50 

40 

85 

64 
68 
63 



No pain. 

No pain for two days. Temp. 100' 

Colic. 

Colic. 

No colic. 

Distended gall bladder. 

Jaundice. 

No pain. 

Colic. 

Day after colic. 

Jaundice. 

Between attacks. 
Deep jaundice. 



August 25tli. 
August 27th. 
August 31st. 
September 6th, 
September 7th. 



October 1st. 
October 5th. 
Between attacks. 



In colic, proved at operation. 
Recurrent pain and jaundice. 



White Cells at Entrance. 



Between 2,000 and 6,000 



6,000 

8,000 

10,000 

12,000 

14,000 



8,000 
10,000 
12,000 
14,000 
16,000 



cases. 



342 



SPECIAL PATHOLOGY OF THE BLOOD. 



Between 16,000 and 18,000 = 4 cases. 
18,000 " 20,000 = 2 " 
20,000 " 30,000 = 3 " 

Total 73 " 

Average number of white cells, 10,000 + 

CHOLANGITIS AND CHOLECYSTITIS. 

Here the leucoeytosis is well marked whenever the inflammation 
has got beyond the catarrhal stage (see Table L., B), and helps 
us to exclude simple impacted gall stone, with or without colic. 
Cancer may or may not ])roduce leucoeytosis, but does not usually 
increase the fibrin network. It is said by Hayem that cholangitis 
does not increase it. 

Bioodgood {loc. c'lt.) concludes that "in acute cholecystitis the 
leucocytes invariably rise to from 20,000 to 27,000." If no opera- 
tion is done and tlie local symptoms abate, the count falls. In chronic 
cholecystitis (8 cases), the leucocytes were from 5,000 to 12,000 
(i.e., normal). "In cholecystitis with jaundice and stone in the 
common duct" (8 cases) tlie leucocytes were normal (2,000 to 10,- 
000). One patient observed from the beginning of an acute at- 
tack showed a rising leucocj^tosis, which reached 24,000 and then 
fell to 9,000 as the acute local symptoms subsided. Jaundice per- 
sisted and at operation a stone was found in the common duct. 

Table L., B.— Cholangitis. 



No. 


Age. 


Sex. 


Red cells. 


AVhite cells. 


Remarks. 


1 
2 
3 
4 
5 


"21" 

65 


F. 
F. 
F. 
M. 
M. 


4,800,000 
6,400,000 
4,960,000 
4,976,000 


50, 000 
30, 000 
22.000 
14,800 
14.186 
11,000 

9,000 
6,800 
4,400 


Suppurative cholangitis. 

Jaundice and cholsemia. 
Gall-stones ; chills. 


6 




October 20th. Operation October 22d 

Abscess of liver. 
Catarrhal. 

Catarrhal. 


7 
8 


28 
34 


M. 
F. 




6,640,000 
5,592,000 
4,770,000 



I 



Table L., C. — Cholecystitis. 



No. 


Age. 


Red cells. 


White cells. 


Per cent, 
ligemogloblu. 


Remarks. 


1 


24 




26,600 
26,400 


80 


November 3d. Suppurative. 
November 4tli. 


2 


48 




23,000 
15.500 




First dav. Infectious. 
Third day. 


ii 


36 




22.600 


60 


Siippiu-ative. 



ABSCESS OF THE LIVER. 
Table L., C — Cholecystitis {Continued). 



343 



No. 


Age. 


Red cells. 


WWre cells. 


Per cent 
hsemoglobln. 


Remarks. 


4 


32 




15,600 


73 


Gall stones. 


5 


47 




14.100 
17.000 


75 


July 14th. 
July 17th. 


6 


25 




12,200 


60 




7 


58 




10,700 


80 




8 


28 





8,500 


90 




9 


50 




8,300 
46,300 




Ten days later. Suppurative. 


10 


44 


3,602,000 


6,600 


50 


Typhoid. 


11 


47 




6,400 


75 


Chronic. Dife. count 400 
cells: Polynuclear, 69 per 
cent ; small lymphocytes, 
29 ; large lymphocytes, 1.5 ; 
eosinophiles, 5. 



The blood does not differ from that of cholangitis with suppura- 
tion. 

ABSCESS OF THE LIVER. 

In most acute cases leucocytosis is well marked (as in 5 of my 
8 cases), but in the chronic latent cases when we most need the 
assistance which leucocytosis might give in diagnosis, it is often 
absent altogether. Thus Osier * in 5 cases found : Case I. 6,000 
to 11,000; Case II. 8,000 to 11,000; Case IIL, 9,000; Case lY., 
15,000; Case Y. , 22,000. Scott" reports on 3 cases and finds that 
the leucocytosis is valueless for diagnosis since it is present only in 
early acute stages when other clinical data suffice, and in chronic 
cases is slight or absent. Cohen ^ reports 13,400 in a chronic case 
with several quarts of pus. Delaney (see reference page 472) in 3 
cases found 15,400, 15,700, and 12,500. Boinet's* 2 cases were 
acute and showed well-marked polynuclear leucocytosis. 

Futcher ^ reports that the average blood count in fifteen cases of 
amoebic dysentry complicated by abscess was as follows : red cells, 
4,250,000; leucocytes, 18,350, and hgemoglobin 66 per cent, "The 
leucocytosis was not a high one. The average was 7,750 higher 
than in the uncomplicated dysentery cases. There were two cases 

' Osier: Med. News, April 12th, 1902. 

2 Scott: Trans. College of Phys., 1902, p. 174. 

3 Cohen: Ibidem, p. 170. 

^Boinet: Soc. des Hop., 1900, p. 1089. 

5 Futcher: Journ. Am. Med. Assn., August 22d,1908. 



344 



SPECIAL PATHOLOGY OF THE BLOOD. 



in which the highest count was under 10,000. Tlie highest leuco- 
cj^tosis of all was 53,000. 

'' Some observers hold that there is a great increase in the leuco- 
cytes in cases of aoembic hepatic abscess and emphasize its impor- 
tance in the diagnosis of such cases. Few, however, give counts 
supporting their statements. Although this series shows that the 
average leucocyte count in the amoebic abscess cases is considerably 
above that in the uncomplicated cases, yet it is doubtful whether 
the leucocyte count is of any great value as a means of diagnosis. 
For instance, in the forty-three uncomplicated dysentery cases there 
were ten in which the leucocyte count was above the average in the 
abscess cases. In two of these the counts were 40,000 and 47,000 
respectively. 

" The average differential count of the leucocytes showed a rela- 
tive increase in the polymorphonuclears. Considering the rather 
large number of eosinophiles seen in the stools in certain cases, it 
was thought that there might be some change in the relative per- 
centage of these cells in the blood. With the object of determining 
whether there Avas such a change or not, Dr. McCrae made differen- 
tial counts in a number of cases, but found the eosinophilic cells 
present in practically normal percentages." 









Table LI.- 


-Abscess 


OF THE Liver. 










White 


Per cent 


o' 


Age. 


Sex. 


Red cells. 


cells. 


baemo- Remarks. 


2; 










grlobin. 


1 


20 


M. 


4,533,000 


33,200 
48,000 


January 11th. 

January 14tli. Operation. 


2 


15 


F. 


3,750,000 


26,800 


. Operation. 


3 


55 






18,900 
23,400 
25,900 
27,000 


85 i Multiple. December 17th. 

1 Perihepatitis. December 19th. 
j December 20th. 
i December 21st. 










17,300 




December 23d. 










28,400 




December 2oth. 










24,400 




December 26th. 










15,000 




December 27th. 










16,800 




December 29th. 










18,000 




January 3d. 










16,800 




January 5th. 










16,200 




January 7th. 










16,400 




January 9th. 










18,000 




January 11th. 










16,600 




January 13th. 










11,700 




January 15th. 










21,900 




January 25th. 










30,600 




January 27th. 



HEMORRHAGIC PANCREATITIS. 
Table LI. — Abscess of the Liver {Continued) 



345 











White 


Per cent 




-J 


Apfe. 


Sex. 


Red cells. 


cells 


hsemo- 


Remarks. 


z 










globln. 












26,000 




January 29tli. 










32,000 




January 31st. 










28,000 


65 


February 3d. 










31,000 


•• 


February 5th, 

February 7th. Operation. 

February 13th. Death. 


4 


60 


F. 


4,460,000 


18,000 




Operation. 


5 


28 


M. 




12,600 






6 


33 


F. 




11.000 
17,500 
19,200 
20,600 


•• 


November 3d. 
November 4th, 11 a.m. 
November 4th, 2 p.m. 
November 5th, 10 a.m. Operation ; 
autopsy. 


7 


26 


M. 


2,664,000 


10,200 
12.000 
15,000 


33 


October 19th. 
October 20th. 

October 21st. October 25th, au 
topsy; streptococci. 


8 


51 


F. 


3,440,000 


9,600 







CANCER OF THE LIVER. 
(See Malignant Disease, page 440.) 

GUMMA OF THE LIVER.' 

Von Jaksch in a single case foimd 2,756,000 red cells, 6,100 
white cells; in similar cases I found 8,900 leucocytes and Grawitz 
17,000. 

DISEASES OF THE PANCREAS. 

HEMORRHAGIC PANCREATITIS. 

Opie records a leucocytosis of 19,600 in a case operated on by 
Bloodgood {Johns Hopkins Bulletin, January, 1901). 

At the Massachusetts General Hospital we have had four cases 
in which the following counts are recorded : 

Acute Hemorrhagic Pancreatitis. 



No. 


^ge. 


White cells. 


Per cent hsemoglobln. 


Remarks. 


1 

2 
3 

4 


26 
50 


9,200 
11,200 
23,000 
24,000 
22,000 


100 


Fourth day. 



346 



SPECIAL PATHOLOGY OF THE BLOOD. 
Chro^iic Pancreatitis. 



Age. 


Red cells. 


White 
cells. 


Per cent 
haemoglobin. 


Remarks. 


56 


2,568,000 


5,600 


52 


November 5th. Diff. count; Poly- 
nuclears, 56 per cent ; small lympho- 
cytes, 36; large lymphocytes, 6.5: 
eosinophiles. 1.5. 




2,680,000 


3,500 

4,500 
6,100 


50 


November 15th. 

November 18th. 

Before test breakfast. 

Four Iiours after test breakfast. 




2,432,000 


2,600 


45 


November 26th. Diff. count 500 cells : 
Polynuclears, 56.4 per cent; .small 
Ivmphocytes, 35.2; large lympho- 
cVtes, 6.8; eosinophiles, 1.6. ' 




2,880,000 


.... 


47 


December 16th. 




2,528,000 





50 


December 29th. 




2,248,000 


5,000 


48 
46 


January 3d. 
January 10th. 



DISEASES AFFECTING THE HEART. 

PERICARDITIS. 

(See Inflammation of Serous Membranes, page 282.) 

ENDOCARDITIS 

In many cases of acute endocarditis the blood shows no changes. 
In others, whatever alterations there may be are covered up by 
those involved in the rheumatic arthritis associated with the endo- 
carditis, 

ULCERATIVE ENDOCARDITIS. 

In ulcerative or malignant endocarditis, we may find the signs of 
a pyogenic infection (see page 237). Sometimes pyogenic cocci can 
be cultivated from the blood, and if present may he of the greatest 
value in a diagnosis always difficult to make. 

Grawitz goes so far as to say that in doubtful cases repeated 
negative results of cultures from the blood make it unlikely that 
ulcerative endocarditis is present. 

Sittmann ^ considers that important help may be given as to the 
position of the primary focus of infection by the nature of the or- 
ganism present in blood cultures — i. e. , the pneumococcus pointing 
to the lung, the colon bacillus to the intestine, etc. 

^ Loc. cit. 



ULCERATIVE ENDOCARDITIS. 347 

Red Cells. 

As in all forms of septicaemia marked ansemia rapidly develops, 
more rapidly probably than in any other disease. The haemoglobin 
loses about equally with the corpuscles, according to most observers 
since blood destruction is so rapid. 

Further evidence of rapid blood destruction is seen in the hsemo- 
globinaemia often present. 

Eoscher (loc. cit.) records counts of 4,400,000 and 2,750,000, 
both fatal cases. 

White Corpuscles. 

Eieder reports a single case showing these variations : 

Temperature. White cells. 

January 2d, 1891. 105= 17,000 

3d, 1891 , 99° 13,700 

8th, 1891 103° 15,500 

10th, 1891 101.5° 18,000 

12th, 1891. 101.5° 21,300 

18th, 1891 101° 18,800 

22d, 1891 104.5° 13,000 

Februarj^ 11th, the patient died. 

Pee found leucocytosis. Eoscher in two cases found : Case I. : 
8,800 leucocytes; the patient died in two days. Case II. : 16,800 
and 12,000. Krebs in one case found : October 27th, 15,500; Oc- 
tober 28th, 44,200; the patient died the same day. 

Twenty-six cases were studied at the Massachusetts General 
Hospital with the following results : 

Table LII. — Ulcerative Endocarditis. 



c 


A„^e. 




Red cells. 


White 
cells. 


Per cent 

hsemo- 

p:lobln. 


Remarks. 




21 






34,300 
39,200 
27,000 
47,600 

30,100 
15,800 
18,100 




Third day. 
Tenth day. 

Seventeenth day. Died twenty- 
first. No autopsy. 
May 27th. 
May 30th. 
June 17th. 


2 


8yrs. 


. . 


4,216,000 


26,100 


50 


N"ovember20th^ 


3 


11 mos. 







27,000 
27,500 





November 23d k .- ^ 
November 27th I ^^^^.f ^\^^^^'^, 
December 3d ^ Mitral msuf- 
December 9th ^^^^^^J- 
December 22d 










27,400 












25,000 













16,600 


.... 



348 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table LII. — Ulcerative Endocarditis {('ontinneil). 











White 


Per cent 






Age. 


i< 


Red cells. 


cells. 


haemo- 


Remarks. 


z 




^ 






globin. 












25,700 

27,840 
18,100 
22,000 


.... JMav 22d. 
.... ;May 24th. 
.... 'May 26th. 
.... ^AIay 28th. 


4 


37 






24,500 

21,300 
16,300 
22,000 


80 


December 15th. Acute malig- 
nant ; pneumococci ; chronic 
fibrous endocarditis ; mitral 
regurgitation; resolving pneu- 
monia; autopsy. 

December 18th. 

December 20th. 

December 22d. 


5 


29 






22,800 






6 


18 






22,700 
20.400 




Autopsy. 


7 


27 






20,300 


75 


(Six mouths' fever.) 


8 


52 






20,100 
13,500 
10,900 
17.400 


80 


July 31st. 
August 4tli. 
August 6th. 
Augu.st 16th. 








4,976,000 


15,900 

12,900 
19,500 
32,300 
18,300 
17.100 
14,800 
13,600 


ro' 
.... 


August 17th. Diff. count 200 
cells. Polynuclear, 89.5 per 
cent: small lymphocytes, 6; 
large lymphocytes, 4; eosino- 
philes, 5. 

August 22d. 

August 26th. 

August 27th. 

August 30th. 

September 1st. 

September 6th. 

September 9th. Autopsy. 


9 


29 






19,100 


.... 


Autopsy. 


10 


35 






18,900 
31,300 

20,400 
20,900 
40.400 
31,000 
37,400 
63.700 
37,150 




Pneumonia, January 28th, 1899. 
February 4th, 1900. No signs but 

a systolic murmur and chills. 
February Uth. 
February loth. 
February 21st. 
February 23d. 
February 25th. 
March 1st. 
March 4th. 
March 7th. Autopsy. Malignant 

endocarditis. 


11 


63 






18,800 
8,600 

18,300 

29,200 
35,800 


.... 


April 7th. T, 102°. Pneumonia. 
April 10th. Pneumonia a:oue. 

T. 99°. 
April 14th, 8 a.m. T. 104. 5^ 

Aortic and mitral. 
6 P.M. 
April 15th, 7 a.m. Culture of 

blood (14th). Pneumococci. 



ULCERATIVE ENDOCARDITIS. 



349 



Table LII. — Ulcerative Endocarditis {Continued). 











White 


Perc 


ent 


o 


Age. 


X 


Red cells. 


cells. 


haerri 


0- Remarks. 


2; 




0^ 






glob 


in. 


12 


27 






18,500 

15,000 
12,000 
15,000 
11,000 
16,000 
13,000 
18.000 
19.500 
16,000 
11,000 
14,800 
13,000 


75 
70 


May 10th. Subacute glomerulo- 
nephritis. Autopsy, 
. May 15th. 
. May 17th. 
. May 20th. 

May 23d. 
. May 25th. 
. May 27th. 

June 4th. 

June 6th. 
. June 9th. 

June 13th. 

June 21st. 
. June 29th. 


13 


34 






18,000 
11,600 
21.400 
16,200 
1,600 
1,300 
24,400 


"so 


February 13th. 

February 16th. Autopsy. 
. February 19th. 
. February 20th. 
. February 23d. 
. February 27th. 
. March 3d. 


14 


23 






17,800 
36,800 
25,400 
25,000 
28,100 
29,400 




. April 22d. Death. 

April 25th. 
. April 30th. 
. May 2d. 
. May 5th. 
. May 7th. 


15 


35 




2,718,000 


15,200 


25 


Polynuclear, 86 per cent. 
Lymphocytes, 14 " 
Eosinophiles, " 


16 


3 yrs. 
11 mos. 






13,500 




No autopsy. • 


17 


44 




3,996,000 


13.400 
18,000 
12,600 
14,500 
20,400 
24,000 


55 


October 18th. 
. October 22d. 
January 13th. 
January 14th. 
January 16th. 
January 18th ; died. 


18 


21 




5,330,000 


11,300 
9.000 
11,700 
18,700 
13,900 


'45 

42 
50 

48 


January 8th. 

Pulmonary embolism. 

March 15th. 

April 6th. No autopsy. 


19 


30 


' ' 




11,000 
31,000 
16,000 


70 


April 2d. 
. April 24th. 
. April 26th. 


20 






3,792,000 


10,000 


'58 




21 


.... 


•' 




8,900 


55 


Autopsy. 


22 


30 






8,460 
8,130 

6,880 


82 


February 23d. T. 101.4°. 
. February 26th. T. 104.8°. 
. February27th. T.103.5^ Death. 


23 


28 






7,900 


. . . 


Hyperplastic. 


24 


32 







7,600 




Autopsy. 



350 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table LII. — Ulcerative Endocarditis {Continued). 









White 


Per cent 




z 


Age. 


1 


Red cells. cells 


haemo- 
globin. 


Remarks. 


25 


23 




3,884.000, 5,200 


45 


December 15th. 














Polvuuclear. 91.2 per cent. 














Lymphocytes. 6.7 " 














Eosiuophiles. 2.1 










11,900 




December 27th. 








4,272,000 


10,166* 

8,800 


50 


December 31st. 
January 7th. 
January 14th. 








3,560,000 


"21,366* 

15,100 

6,200 


'45' 


January 15th. 
January 26th. 
January 30th. 
February 24tli. 








2,852,000 


9,800 


35 


March 8th. No autopsy. 


26 


38 




3,652,000 


3,000 


50 


Polynuclear. 77.0 per cent. 
Lymphocytes. 22.5 
Eosiuophiles, .5 
No nucleated reds. Autopsy. 



Practically the same are the coimts in the following cases of 
apparently " benign " endocarditis with fever and rapidly shifting 
murmurs, the tenth complicating chorea in a boy of thirteen. 

Table LIIL — "Bexign" Endocarditis. 











White 


Per cent 




^• 


Age. 


sex. 


Red cells. 


cells. 


haemo- 


Remarks. 


2 










globin. 




1 


56 


F. 




50,100 
35.800 




Xovember 24th. 
Xovember 27th. 






i 


36,600 


. , 


Xovember 30th. 










22,800 




December 7th. 


2 


23 




1.424,000 
1,240,000 


31.600 
28,000 


25 
26 


December 10th. 
December 13th. 
December 15th. Death. 


3 


4 






29,600 
28,500 
19.600 


" 


Twenty-first. Temp. 102'. 
Twenty-second. Temp. 98°. 
Twenty-fifth. 


4 


25 







26,600 
41,200 
32,300 


70 












29,300 
28,400 












32,200 




October 27th. 










27.300 




October 28th. 










29,000 




October 30th. 










24,200 




Xovember 3d. 










29.600 




Xovember 5th. 










28,200 




Xovember 8th. 










36.500 




Xovember 13th. 









a 


BENIGN 


" ENDOCARDITIS. 6bl 


Table LIII. — "Benign" 'E^docauthtis (Continued). 


6 
2i 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haBino- 
globin. 


Remarks. 


5 


28 


•• 




24,800 
11,700 




Twenty-fourth. 
Twenty-lifth. 


6 

1 


11 




4,728,000 


24,500 
17,700 


55 


Fh'st day. 
Seventh day. 


1 






14,000 


55 


Fourteenth day. 










15,100 














10,800 


55 












10,100 


34 




7 27 






24,000 


80 


First day. 


j 




1 16,000 




Fourth day. 








13,600 




Fifth day. 


8 


13 






22,500 
15,200 
21,400 
18,400 
29,400 


80 

85 


January 28th. 
February 1st. 
February 4th. 
February 8th. 
February 21st. 


9, 29 






21,320 




Pregnancy four months. 


10 13 


M. 




20,600 
17,900 
18,700 
16,800 
21,200 
27,400 
22,700 


62 


May 26th. Temp. 102°-104°. 

May 29th. 

May 31st. 

June 3d. 

June 4th. 

June 8th. 

June 11th. 










24,200 




June 13th. 










21,900 




.June 15th. 










26,100 




June 17th. 










26,800 




June 19th. 










17,400 




June 23d. 










28,700 




June 26th. 










21,200 




July 2d (outdoors). 










21,300 




July 4th. Left the hospital July 
19th. 


11 


54 


•• 


3,768,000 


20,200 
24,400 


90 


-January 24tli. 

January 26th. Autopsy. 


12 


17 






19,800 
19,200 




December 16th. Mitral insutfi- 

ciency. Renal colic. 
December 20th. 


13 


34 






19,700 
12,900 
11,000 
10,500 
7,200 
14,500 
19,300 
14,200 
18,300 
14,400 
10,200 
24,000 
35,300 


50 . 
52 


November 5th. 
November 7th. 
November 9th. 
November 12th. 
November 14th. 
November 22d. 
November 25th. 
November 28th. 
November 30th. 
December 2d. 
December 5th. 
December 8tli. 
December 11th. 


14 


26 


•• 





12,000 




Salpingitis. 



352 



SPECIAL PATHOLOGY OF THE BLOOD. 



Diagnostic Value 
(a) Blood cultures should never be omitted iu cases of suspected 
malignant endocarditis. When positive they are of great value. 
(b) In excluding typhoid, malaria, and miliary tubercle the pres- 
ence of leucocytosis is important. I saw within a few months a 
case in which several consultants had made the diagnosis of typhoid, 
but in which the presence of marked and persistent leucocytosis and 
the absence of a typhoid serum reaction convinced me that the case 
was one of ulcerative endocarditis. This has since been verified. 

MYOCARDITIS. 

Whenever stasis and disturbance of the circulation result from 
weakness of the heart wall, blood changes identical with those de- 
scribed under Valvular Heart Disease are present. Otherwise the 
blood is normal. The ordinary findings are shown in the following 

tables : 

Table LIV., A. — Myocarditis. 



Age. 


Sex. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


51 






30,000 


75 


Xo autopsy. 


54 






13,200 


68 


Mitral di-sease with broken com- 
pensatiou. 


62 






12,900 






58 




4,944,666 


11,800 


45 


Broken compensation. Chronic 
bronchitis. 


60 






10,700 






63 






10,700 




Mitral insufficiency. 


75 






8,800 




Syncope. Chronic interstitial 
nephritis. 


58 






8,300 


68 


Progressive muscular atrophy. 
Arthritis deformans. 


55 






7,400 






68 






7,200 




Chronic interstitial. 


67 







6.700 




Chronic interstitial. 



J 



TABLE LIV., B. 

White cells. Cases. 

Between 4,000 and 6,000 2 

6,000 " 8,000 11 

8,000 " 10,000 11 

10,000 " 12,000 12 

12,000 " 14,000 7 

" 14,000 " 16,000 7 

16,000 " 20,000 3 

20,000 " 26,000 5 

Total 58 

Average count of white cells 9,100 



VALVULAR HEART DISEASE. 353 

VALVULAR HEART DISEASE. 

Grawitz divides valvular heart disease into three stages with 
corresponding blood conditions : 

1. Stage of full compensation : blood normal. 

2. Stage of acute failure of compensation : blood diluted (Oer- 
tel's *•' plethora serosa''). 

3. Stage of chronic stasis and cyanosis : blood concentrated for 
the most part; at times diluted as well. 

1. A valvular lesion ^^er se has no effect on the blood. 

2. When compensation fails and blood pressure is lowered, we 
find (^especially in the venous hlood) that the fluid from the sur- 
rounding h^mph spaces has made its way into the vessels and diluted 
the blood. The specific gravity falls, red cells and haemoglobin are 
lower than before, while the white cells are unaltered, and the 
plasma is shown to be more watery than before, as well as of in- 
creased quantity per cubic millimetre. All these changes are less 
marked in capillary blood, and hence are rarely observed. 

3. If the heart adjust itself partially to the increased work it 
has to do, and to the chronic passive congestion of the internal or- 
gans and at the periphery, the blood is concentrated, probably in 
part by transudations into serous cavities and lymph spaces, and 
in part by the increased excretion of moisture b}' the lungs. The 
specific gravity and the number of red cells are increased, especially 
in the capillaries, and to a less extent in the venous blood (the con- 
ditions being just the reverse of those in acute heart failure, stage 
No. 2). This is the condition usually found in heart disease with 
chronic venous stasis (passive congestion). 

But this concentrated condition of the blood may be offset from 
time to time by fresh weakening of the heart and lessening of blood 
pressure, and the combination of the two conditions may result in a 
normal blood count. 

The condition of concentrated peripheral blood with the count 
of red cells above normal is that most commonly seen in chronic 
heart disease with stasis.^ 

Yon Limbeck finds that aortic lesions are more apt to show a 
normal or diminished blood count, while mitral disease is more apt 
to be accompanied by the temporary dilutions and long-standing 

'Gibson (Brit. Med. Jour., January ITtli, 1903) has recorded some striking 
cases ilhistrating this point. 
9fl 



354 SPECIAL PATHOLOGY' UF THE BLOOD. 

concentration above described. He does not explain the cause of 
this, and it does not coincide with my cases. One of his patients 
with double mitral lesion showed a decrease of 1,170,000 red cells 
(from. 7,500,000 to 6,330,000) after exertion. When the patient 
was quiet, the lesion was compensated; on exertion compensation 
temporarily failed, blood pressure was lowered and the blood 
diluted. 

Sadler ' found considerable anaemia in three out of four cases of 
aortic disease, while only two of seven patients with mitral lesions 
showed anaemia. 

Schneider's "^ results were similar in that he found the red cells 
normal in the aortic cases and increased in the mitral ones. 

Hayem found anaemia most common in aortic regurgitation, espe- 
cially in young people. 

In the Massachusetts General Hospital records there have been 
a strikingly large number of cases of mitral disease associated with 
severe anaemia (see cases 2, 10, 14, and 88 of Table LV.). The 
counts of red cells in twenty cases average 3,400,000, and nucleated 
red cells were found in three cases. These were all of them sujj- 
posed to be chronic cases without any active endocarditis, septic or 
benign, and were for the most part afebrile. In view of the marked 
anaemia and leucocytosis, however, I am in doubt whether the endo- 
carditis was really as dormant as the temperature and the absence 
of chills or embolism would suggest. 

In cases of aortic disease due to arteriosclerosis, there was no 
considerable anaemia or leucocytosis. 

White Corjmscles. 

Almost all writers whom I have consulted agree that the leuco- 
cytes are normal unless some complication occurs. Yet in a large 
number of the Massachusetts General Hospital cases the leucocytes 
were steadily hicreased, while the red cells were diminished (see 
Table LV.) This leucocytosis cannot be explained as the result of 
I stasis, since it is rare in aortic disease or in myocarditis, despite 
stasis, and is found chiefly in mitral cases. That stasis plays a part 
in the blood counts of congenital heart disease seems evident from 
the cases next to be mentioned, in which the red cells are increased 
only about forty per cent, while the white are often one hundred 
per cent more numerous than normal. 

1 Loc. cit., p. 33. -2 Inaug. -Dissert., Berlin, 1888. 



VALVULAR HEART DISEASE. 



355 



The apparently normal count of red cells in. some of our cases 
may have been due to the coverhig up of an ansemic or diluted con- 
dition of the blood by concentration, the resultant of the two forces 
being an apparently normal count. 

In the 91 cases of mitral disease tabulated on pages 356-358, 
there are 51, or 56 per cent, showing leucocytosis of more than 
11,000, and 32 with over 16,000 leucocytosis. In some of the 
cases there was pulmonary infarction or nephritis as a complication, 
and these lesions may have influenced the count. 

The polynuclear cells are proportionately increased. In expla- 
nation of the anaemia and leucocytosis of mitral disease and the lack 
of these phenomena in aortic disease, I conjecture that mitral dis- 
ease is rarely long dormant, and that the " failures of compensa- 
tion," for which my cases sought the hospital, were associated with 
or due to fresh vegetative or thrombotic processes on the valves. 

(Edema and diuresis have in themselves little or no constant 
effect upon the blood, as a recent observation of Petrowsky's has 
demonstrated. 

CONGENITAL HEART DISEASE. 

Vierordt ^ has collected the following table of cases of congeni- 
tal heart disease showing extreme polycy thsemia : 



Toeniessen,2 1889 

Toeniessen,"^ 1889 

Krehl.3 1889 

Moritz/1892 

Vaquey,^ 1893 

Bauholzer,« 1894 

Carmichael,'' 1894 

Hayem,« 1895 

Gibson,^ 1895 

J. Thompson ''^^' (and Gibson). 



Specific 
gravity. 



1.071 
1.081 

l.O'H 



Red cells. 



820, 
540, 
100, 
900, 
900, 
447, 
100, 
500, 
470, 
700, 



000 
000 
000 
000 
000 
000 
000 
000 
000 
000 



White 
cells. 



8,800 



16,000 

9,900 

12,000 

12,000 



Per cent 
hfemo- 
globin. 



150-170 
160 



110 
92 



Age. 



13 
10 
23 

24 

40 
10 
? 

25 

8 

2 



Sex. 



F. 
M. 
F. 
]VL 
M- 

V 

M. 
M. 
M. 



'Vierordt: Notlmagel's SpeciellePatliologie und Tlierapie. 

- Toeniessen : Dissertation, Erlangen, 1881. 

3Krehl: Deutsch. Arch. f. khn. Med., 1889, p. 426. 

^Moritz: Cited from Vierordt. ^Vaquey: Soc. de Biol, May, 1892. 

^Bauholzer: Cent. f. inner. Med., 1894, p. 531. 

■' Carmichael : Edin. Hosp. Rep., 1894, vol. ii, 

^Hayem: Med. moderne, 1895, p. 397. 

9 Gibson: Lancet, 1895. vol. i., p. 24. '"Thompson: Cited by Gibson. 



356 



SPECIAL PATHOLOGY OF THE BLOOD. 



Nouille,' 1896 
Ruge,2 1897 . . 
Kovacs/^ 



Specific 
gravity. 



1.077 



Red cells. 



8,570,000 
6,800,000 
9,600,000 



White 
cells. 



Per cent 
haemo- 
globin. 



Age. 



Townseud ' studied 14 cases. In 7 cases under one year tlie 
counts were 11,800,000, 8,051,000, 8,000,000, 7,144,000, 6,580,000, 
6,570,000, and 5,900,000. In 5 cases between the first and twenty- 
fourth year the counts were 9,950,000, 8,590,000, 7,590,000, 
6,570,000, and 6,000,000. In 2 cases tlie count was not increased; 
one of these showed no cyanosis. 

How such cases are to be explained I do not know; the ordinary 
explanation of concentration of the blood will not hold in cases in 
which no stasis or lack of compensation exists, yet the skin is blue 
and the blood counts are enormous. 

Tliere is no doubt that the peripheral capillaries always contain 
more corpuscles per cubic millimetre than do the veins. Numerous 
reports from various oV)servers agree upon this. Whether this is 
on account of the loss of water by perspiration and consequent drain 
of blood from the skin capillaries is uncertain, but in congenital heart 
disease both capillary and venous blood are overcrowded with cor- 
puscles and the explanation is difficult. Hayem in a case of this sort 
reports 7,000,000 red cells with a decrease in the average diameter. 

Table LV. — Mitral Valve Disease and Its Complications. 



< 

26 
39 

30 
44 


i 


Red cells 


White 
cells. 


ll 


Lesions. 




Mitral. 


Aortic. 




Remarks. 




3,448,66ft 
3,596,000 

4,480,666 


44,000 
43,150 

8,800 

32,000 

20,400 

27,000 


70 
55 

43 

62 

40 


M. 
M. 

M. 

Ruptured 

comp. 

M. 


A. 




Died same day. 

July 5th. Polynuclear, 71.4 ; lympho- 
cytes, 27; myelocytes, 6; masts, 4. 

July 9th. July 10th, autopsy. Fresh 
and old endocarditis. 

Temp., 100°. 

Fifth day. Purpuric spots. 



iNoullle: Th^se de Paris, 1896. 

2Ruge: Berliu. klin. Woch.. 1897, p. 429. 

=^Kovacs:. Cit. by Koranyi, Zeit. fiir khn. Med., 1887, vol. xxxl 

•^Townseud: Archives of Pnpil., September, 1899. 



CONGENITAL HEART DISEASE. 357 

Table LV.— Mitral Valve Disease and Its Complications {Continued), 









Red ceUs 


White 
ceUs. 


11 
21 


LESIONS. 










1 '^ 


Remarks. 


.. 


^ 


>< 








Mitral. 


Aortic. 


s| 




'^ 


< 
32 


^ 












S 




5 






30,000 




M. 
















19,000 










First day with infarcts. Temp., 103°. 


6 


31 







23,000 


78 


'm.* 




T. 


Third day. Died on fifth. 




36 






22,600 

22,600 
24,600 
19,000 




M. 
Double. 


A. 

•• 




No fever. 

Fourth day. 
Sixth day. 
Seventeenth day. 


8 


23 






22,400 




'm." 




T. Pulmonary infarction. 


9 


8 






22,100 




M. 






lu 


8 




2,624',666 


22,000 


35 


M. 




. . : With nephritis. Polynuclear, 88 ; lym- 
phocytes, 12; eosinophiles, 0; 3 
normoblasts. (Count 500.) Died. 


11 


19 







20,800 
11,700 


65 


M. 

Stenosis. 




. . Four days later. Temp., 96°. 


12 


25 




3,756,000 


20,700 


35 


M.- 


A. 
Double. 


. . April 10th. 








3,680,000 


13,000 


35 


.... 


.. April 20th. Temp., 104.6°. (Count 500.) 


















Polynuclear, 86.6 per cent.; small 


















lymphocytes, 8.6 ; large Ij^mphocytes, 
















j 4.4 ; eosinophiles, .2 ; myelocytes, .2 ; 
















1 1 normoblast. No autopsy. 


13 


50 


... 




20,500 


75 


M. 




. . Dilated and hypertrophied with pul- 
monary infarct. 


14 


16 


F. 


2,672,000 


20,500 


42 


M. 


A. 


. . Acute nephritis. 


15 


76 




20,400 




M. 


! . . Cerebral embolism. 


16 


40 






20,000 

15,000 
10,4(K) 


76 


M. 
Double. 


1 .. 


Third day. 
Seventh day. 


17 


45 




3,244,000 


19,900 


35 


"m." 


! . . 


No autopsy. 


18 


39 







19,700 


55 


M. 

Stenosis. 
M. 




With acute nephritis. 


19 


25 


... 




19,600 






Pulmonary infarction ; bloody pleurisy. 


20 


38 


M. 


3,648^666 


19,300 


45 


M. 

Stenosis. 
M. 


1 


Albumin one-fourth per cent. 


21 


22 


... 




19,000 








With nephritis. 


22 


35 






19,000 


72 


M. 






Broken compensation. 


23 


35 






18,000 




M. 








24 


9 




4,i.6b',666 


18,000 
23,000 
30,000 


60 
55 
65 


M. 






First day. Temp., 197°. 

Thirteenth day. 

Twenty-second day. Hydrothorax. 


25 


54 






18,000 


65 


"m." 




Temp. 98°. Died. 


26 


22 






17,900 


80 


M. 






2T 


30 






17,100 


65 


M. 




No fever. 


28 


40 






16,800 


65 


M. 




Temp., 101°+. 


29 


64 






16,400 




M. 




Pulmonarv infarction. 


30 


5 




3,808,666 


16,000 


45 


M. 


1 . . 


Temp., 99.5°. 


31 


34 






16,000 
11,000 
21.000 


68 


M. 


\ '.'. 


First day. 

Seventh day. Temp., 101'. 

Eighth day. 










14,2(X) 




.... 






Fourteenth day. 










9,400 




. . . 






Thirty-fifth day. 


32 


56 






16,000 


60 


M. 


A. 






:)3 


47 






15,400 




M. 


A. 




Temp., 99-100°. 


34 


30 




3,840,000 


15,300 
8,600 
15,000 


38 
43 


M. 


A. 




First day. Temp., 99". 
Eleventh day. 
Temp., 97°. 


35 


38 






14,100 


6.5 


*M." 




t. 




36 


27 




> 


14,000 
13,000 


100 


M. 


A. 


T. 


First day. 
Third day. 


37 


il 


... 




14,000 




M." 


A. 




With diffuse nephritis. 


:38 


^ 






14,000 




M. 






Temp., 98°, with myocarditis. 


;39 


34 







13,400 




M. 






Temp., 98°, with nephritis. 


40 


58 




3,814,000 


13,400 


50 


M. 


A. 




Temp., 98°. 


41 


50 


,. 




13,200 


55 


M. 








42 


19 




3,82b",666 


13.100 


.55 


M. 








43 


52 


... 


4,876,000 


12,800 


60 


M. 


A. 




Temp, usually subnormal. 



358 SPECIAL PATHOLOGY OF THE BLOOD. 

Table LV.— Mitral Valve Diseases and its Complications {^Continued). 













White 
cells. 


i! 


LESIONS. 






Red cells 






TJ 


Remarks. 












^ S 






■cK 




i 


21 


>< 








Mitral. 


Aortic. 


^i 




u 






12,800 




M. 


A. 






45 


28 






12,800 


60 


M. 


A. 






46 


52 






12,500 


80 


M. 


A. 






47 


41 






12,1(X) 




M. 








48 


25 




i'mM) 


11,400 


45 


M. 


A. 




Temp., 98°. 


49 


46 




4,500,000 


11,200 


40 


M. 


A. 




With angina. 


50 


21 


... 




11,200 


52 


M. 

Double. 








51 


48 






11,200 


65 


M. 








52 


68 






lum 




M. 






Temp., 98». 


53 


34 






11,000 




M. 








54 


33 






10,700 65 1 


M. 






Temp., 98°. 


55 


45 







10,600 




M. 


A. 






56 


54 






10,600 


72 


M. 






Asthma. 


57 


43 






10,200 


77 


M. 






Broken compensation. 


58 


40 






9,900 




M. 


A. 




Temp, subnormal. 


59 


19 






9,900 




M. 






Temp., 98°. 


60 


27 






9,900 




M. 








61 


25 






9,800 


76 


M. 


A. 






62 


40 






9,600 




M. 








63 


28 






9,600 




M. 


A. 




Temp., 98°. Broken compensation. 


64 


20 






9,500 


76 


M. 

Double. 






Temp., 100°. 


65 


39 






9,400 


65 


M. 






Broken compensation. 


66 


54 






9,4(M) 




M. 






Broken compensation. 


67 


27 




5,360,666 


9,200 100 


M. 








68 


49 






9,2(X) i . . 


M. 


A. 






69 


33 







9,000 1 72 


M. 








70 


27 






9,000 . . 








December 14th. 








6,452,666 i 95 1 








Deceinlier 21st. 


71 


61 




4,953,000! 8,900 


48 


M.' 






Brok(^n coiupensation. No autopsv. 


72 


49 




1 8,8(X) 


60 


M. 






Temp., 98°. 


73 


46 






i 8,800 




M. 








74 








1 8,600 




M. 


A. 




Fever. Gonorrhoea (?). 


75 


46 








8,500 




M. 






Temp., 97°. 


76 


40 








8,400 




M. 






Temp., 96°. 


77 


40 








8,200 1 .. 


M. 






Temp., 98°. 


78 


38 








8,000 ; . . 


M. 


A. 






79 


36 








7,900 .. 


M. 






Broken compensation. Temp., 97°. 


80 


41 








7,900 




M. 




















Stenosis. 








81 


50 






7,800 




M. 






Temp., 97°, 


82 


44 




4,b4b",666 


7,500 


55 


M. 
Double. 








83 


49 






7,300 




M. 








84 


40 






7,000 




M. 








85 


28 






6,800 


[[ 


M. 








86 


32 






6,600 


•• 


M. 

Double. 








87 


50 






6,000 




M. 








88 


30 




i,6ob',666 

1,536,000 


6,000 

4,200 


16 
10 


M. 


A. 




First day. Polynuclear, 61.6; lympho- 
cytes, 38; eosinophiles, 4; megalo- 
blasts, 1 ; normoblasts, 8 ; reds pale, 
large, deformed. 

Seventh day. Polynuclear, 67; lym- 
phocytes, 32 ; eosinophiles, 1 ; megal- 






































oblasts, 4; normoblasts, 7. Large 




















oval forms. 








1,728,000 


10,400 


15 


.... 






Fifteenth day. 








1,720,000 


5,000 


m 








Twentieth day. Polynuclear, 71; 
lymphocytes, 27; eosinophiles, 2; 
megaloblasts, 1. 








1,840,000 


5,200 


18 


.... 






Twenty -seventh day. 


89 


59 






6,000 




M. 


A. 






90 


40 


... 




5,800 


70 


M. 






Temp., 98°. 


m 


40 


... 




4,900 




M. 


A. 







i 



CONGENITAL HEART DISEASE. 



359 



Mitral Valve Disease and Its Complications. 
Summary. 

Wbite cells. Cases. 

Between 2,U00 aud 6,000 7 

6.000 •• 8,000 41 

8,000 " 10.000 46 

10.000 " 12,000 42 

12.000 " 14,000 38 

14.000 " 16.000 23 

16.000 " 18,000 23 

18,000 •' 20,000 19 

20.000 •' 22,000 8 

22.000 •■ 24.000 9 

24,000 •• 30,000.. 8 

30,000 or more 6 

Total 270 

Average 13,000 -j 

Total over 14,000 = 96 cases, or thirty-five per cent of all. 

Table LVI. — Aortic Valve Disease. 



1 : 






White 


Per cent 






A?e. 


Sex. 


Red cells. 


cells. 


hsemo- 


Remarks. 


Z 










globln. 




1 


42 






31,000 


50 




9, 


95 








30,600 


80 




3 


18 
26 








22.000 
20,400 


70 
95 




4 






Cerebral embolus. 


5 


4S 








19 900 


80 




6 


54 








16 300 


75 


Chronic nephritis. Autopsy. 
Chronic nephritis. 


7 


26 








13.700 


60 


« 


? 








12.800 


67 




9 


52 






.... 


12.000 


60 


First day. Temp. 101°. 










20.000 




Third dav. Temp. 102^ 










26,000 




Sixth day. Temp. 102^ 










25,000 




Eighth day. Temp. 101''. 










30,000 




Fourteenth day. Temp. 101'. 










21,600 


.. 


Twentieth day. Temp. 99.3". 
Twenty-seventh day. Autopsy. 


10 


22 

40 






11,600 
9,700 


85 
70 




11 







^9 


24 

38 I 






9,200 
8,600 


100 

85 




13 






14 


21 







•8,500 


95 




15 


56 






7,800 




Angina. 


16 


33 

57 ! 






7.700 
7.600 


95 

68 




17 






18 


39 i 






7.200 


90 




19 


74 






7.200 


65 




20 


58 






7.10U 


80 




21 


? 






7.000 


68 




22 


24 




5,024,000 


6.800 


60 




2;-^ 


39 
37 






6.600 
6,000 


75 




94 




With chronic diffuse nephritis. 


25 


24 






5.000 




26 


78 






3,200 




Temp. 98'. 


27 


22 




4,400,000 




45 





360 SPECIAL PATHOLOGY OF THE BLOOD. 

The most important practical deduction from these data is that 
a blood count in a patient suffering from poorly compensated heart 
disease has no value in determining whether or not anaemia is pres- 
ent. The actual number of corpuscles in the body is not measured 
by the number contained in a drop of peripheral Ijlood, since anae- 
mia may be effectually masked V)y concentration or simulated by 
dilution . 

This holds good equally for any condition involving general 
stasis and cyanosis either from embarrassment of the heart's action 
or otherwise (for instance, pneumonia in certain stage, emphysema, 
displacement of the heart by serous effusions, or tumors), or local 
stasis of the part from which blood is taken. Penzoldt ' noted that 
in old hemiplegic cases the blood from the affected side contained 
more corpuscles than that from tlie sound side, and the writer has 
noticed the same thing in a variety of vasomotor affections involv- 
ing local asphyxia. 

ANEURISM. 

As a rule I have found the blood entirely normal, but in the fol- 
lowing case it might have thrown light on the diagnosis. A patient 
was recently admitted to the Massachusetts General Hospital with 
an acute affection of the chest, supposed to be pneumonia in spite 
of the slightness of the fever and the irregularity of the physical 
signs. At autopsy a ruptured aortic aneurism was found. The 
blood count had showed 3,324,000 red cells, 20,800 white, and 33 
per cent haemoglobin. The low percentage of haemoglobin and red 
cells was really inconsistent with an acute pneumonia in a man pre- 
viously well, and might have hinted strongly toward the correct 
diagnosis had attention been directed more carefully to the blood. 
After gelatin injections, leucocytosis always appears. 

DISEASES OF THE KIDNEYS. 

Many factors other than the disease itself may influence the 
blood of nephritic cases. For instance, in scarlatinal nephritis the 
long-standing leucocytosis is probably due largely to the scarlatinal 
poison, rather than to the nephritis. The occurrence of large quan- 
tities of blood in the urine has the same influence as any other 
hemorrhage upon the blood. 

' Berliner klin. Woch., 1881, p. 457. 



ACUTE NEPHRITIS. 361 

(Edema as such has apparently very little effect upon the blood, 
but the loss of albumin in the urine tells both on the corpuscles and 
on the serum, thinning both with consequent lowering of the specific 
gravity of the blood. 

ACUTE NEPHRITIS. 

1. Red Cells and Hcemoglohin. 

Whether largely from the loss of blood from the kidneys or from 
other causes, the red cells are often much diminished, but the hae- 
moglobin suffers still more. 

Laache reports an average loss of nineteen per cent of the red 
cells and twenty-six per cent of their coloring matter. 

Hayem found no considerable loss of red cells unless the urine 
was hemorrhagic. The following cases illustrate his results : 

Case I. — Acute nephritis, ending in recovery. 

Red cells. 

March 17th, 1882 3,069,000 

March 31st, 1882 2,759,000 

April 7th, 1882 2,821,000 

May 1st, 1882, albuminuria ceased. 

May 17th, 1882 3,038,000 

May 31st, 1882 3,689,000 

Case II. — Acute (puerperal) nephritis; recovery. 

Red cells. 

April 6th, 1881 2,945,000 

" 9th, 1881 2,976,000 

" 12th, 1881, no albumin in urine. 

" 13th, 1881 3,137,500 

" 20th, 1888 3,310,000 

Case III. — Nephritis (chronic?) with hsematuria. 

Red cells 2,821,000 

(It should be noted that Hayem's counts are low on the average, 
and the instrument used by him was not very reliable.) 

Grawitz in acute nephritis records 3,400,000 red cells at the be- 
ginning of the third week and 3,100,000 ten days later. 

Koblank' counted 5,168,700 in a case of acute nephritis with 
oedema. 

Sadler {loc. cit.) in six cases of acute nephritis found in two 
'Inaug. -Dissert., Berlin, 1889. 



362 



SPECIAL PATHOLOGY OF THE BLOOD. 



cases 3,590,000 and 2,262,000 red cells; in tlie other four practically 
normal counts. 

Pieraccini ' found no appreciable ansemia. 

Table LVII. — Acute Nephritis. 



Af?e. 


Sex. 


33 




18 mos. 




14 




3i 




3 




56 


F. 


33 




35 




46 




18 




32, 




54 




14 




14 




24 




11 


F. 


30 




45 


M. 


42 




40 




40 




20 




13 


F. 


11 




23 


M. 


25 




35 




24 


F. 



Red cells. 



3,568,000 



5,020,000 



4,020. 

4,068, 



000 
000 



3,532, 
4,304. 

4,880, 



000 
000 
000 



White 
cells. 



50,000 
36,000 
31,000 
27,000 
23,000 
22,000 
14,000 
11.900 
12,200 
21,200 
44.800 
32,000 
31,000 
21,000 
25,000 
21,000 
21,000 
29,000 
31,000 
13.000 
11,000 

9,300 
21,000 
17,200 
17,000 
17,000 

6,500 
16,850 
15,200 
15,100 
30,100 
28,600 
22.400 
14,000 
14,000 
13,700 
13,200 
13,000 
12,700 
12,600 
12,500 
12,000 
11,800 
11,700 
11,600 
11,500 
11.100 



Per cent 
haemo- 
globin. 



37 



70 
90 
85 
90 

70 
75 
70 



60 
52 
90 
43 
36 
65 
75 
65 

70 
50 
75 

85 
85 



Remarks. 



Untmia. Septic eudometritis. 
Parenchymatous. 



Temperature 102.5'. 

Sixth day. 

Ninth day temperature faUing. 

Nineteenth day. 

Uraemia. July 13th. 

Lobar pneumonia. July 19th. 

July 22d. 

July 28tli. 

August 2d. 

August 5th. 

August 7t.h. 

August 11th. 

August 13th. 

August 16th. 

August 21st. 

August 23d. 

August 25th. 



Uraemia. August 4th. 
Au£:ust 29th. " 



December 13th. 
December 18th. 
December 19th. 
December 20th. 



Uraemia. 



Pieraccini: "La Morfologia del Sangue nelle Nefriti," Florence, 1901. 



ACUTE NEPHRITIS. 363 

Table LVII. — Acute Nephritis {Continued). 



6 


Age. 


Sex. 


2 






29 






30 


25 




31 


26 




32 


33 


M. 


33 


29 




34 


32 




35 


22 


M. 


36 


38 




37 


22 


M. 


38 


44 


F. 


39 


37 


M. 


40 


13 




41 


25 




42 


55 


• • 


43 


20 




44 


20 


M. 


45 


54 




46 


33 




47 


22 


F. 


48 


20 




49 


39 




50 


40 


•• 



Red cells. 



White 


Per cent 


cells. 


haemo- 




globin. 


10,800 


50 


10,400 


60 


10,400 


70 


9,300 


50 


9,300 


85 


8,700 


85 


8,300 


48 


8,000 


75 


7,600 


60 


7,500 


65 


6,800 


78 


6,800 


85 


6,600 


40 


6,200 




6,200 




6,000 


58 


6,000 


75 


5,900 


60 


6,800 


60 


5,400 




5,100 




5,100 


55 




65 


4,600 


77 

1 



Remarks. 



5,228,000 



3,904,000 



4,300,000 



4,080,000 



5,000,000 

3,"568,bbb 
3,584,000 
4,044,000 

4,090,000 
3,752,000 



Purpura also. 



Parenchy matou s . 

Parenchymatous. 
Acute parenchymatous. 

October 20th. 
November 3d. 

Acute parenchymatous. 



In none of the few cases examined at the Massachusetts General 
Hospital were the red cells much diminished, but in two cases the 
haemoglobin was low, the color index being 0.62 in one and 0.61 
in the other. 

The blood plates are much increased (Hayem) and fibrin is 
slightly increased. 

2. White Cells. 

Leucocytosis is usually stated to be the rale, lasting often for 
weeks at a time and gradually diminishing in convalescence. 

Hayem gives counts of 14,973, 12,400, 15,000, and 13,000. 

Koblank (loc. cit.) and Grawitz each in a single case found nor- 
mal counts (7,300 and 5,600). 

Sadler found an increase in only one of his six cases, and then 
the highest point reached was 13,312. 

Of the fifty cases of Table LYII,, leucocytosis was present in 
twenty-one, in one of which it was followed for three weeks and 
still persisted; but it is my own belief that the leucocytosis of acute 



364 SPECIAL PATHOLOGY OF THE P>LOOD. 

nephritis is due either to complicatious, to loss of blood by tlie kid- 
ney, or to uraemia. When these conditions have been absent I liave 
not found any leucocytosis. This agrees with Pieraccini's results. 



CHRONIC DIFFUSE AND CHRONIC PARENCHYMATOUS 
NEPHRITIS. 

Red Cells. 

In advanced stages the counts may run very low, but more often 
it is chiefly the haemoglobin that suffers. Hayem gives the follow- 
ing figures : 

Case I. — Chronic parenchymatous nephritis. 

Red cells. Per cent Hb, 

June 20th 4.309,000 43 

July 4tli 4,216,000 44 

October 18th 2,945,000 34 

Case II. — Same diagnosis. 

Red cells. Per cent Hb. 

March 6th 2,619,500 36 

8th 2,836,500 36 

28d 2,404.500 27 

Koblank {loc. cit.) in the same disease found 3,291,700 red cells 
in a single case with much oedema. 

Reinert found 4,050,000 with 50 per cent of haemoglobin and 
3,604,000 with 62 per cent of hemoglobin. 

Sadler. 

Red cells. 
Case 1 4,120,000 

f 2,405,000— November- I9th. 
" 2 ^ 1,110,000— Januarv 14th. 

tl.500,000— January 17th. 

" 3 4,300.000 

" 4 4.300.000 

r3,73T.500— .Iune28th. 
" 5 ^ 3,593,700— .lulv 3d. 

[2,187,500— August 15th. 

f3,200,000— Julv7th. 
3.257.000— July 22d. 
3,137,000— Auffust 21st. 



1: 



Grawitz in an acute exacerbation of a chronic parenchymatous 
nephritis found 1,928,000 red cells. Da Costa in a series of 15 



DIFFUSE AND PARENCHYMATOUS NEPHRITIS. 



365 



cases found the red cells from 2,270,000 to 5,520,000 — average 
3,971,000; the hgemoglobin from 30 to 82 — average 57 per cent; 
leucocytes from 4,000 to 16,000— average 8,600. 

The Massachusetts General Hospital cases show a considerable 
anaemia in forty-one out of the sixty-four, or two-thirds of the series. 
Great concentration or cardiac weakness is probably the cause of 
the very high counts in certain cases. The majority of cases are 
not far from normal so far as the number of red cells goes, and the 
haemoglobin is also very little diminished. 

Chronic Nephritis, 

Red cells. Cases. 

Between 1,000,000 and 2,000,000 3 

2,000,000 " 3,000,000 12 

3,000,000 " 4,000,000 26 

4,000,000 " 5,000,000 14 

5,000,000 " 6,000,000 6 

6,000,000 •' 7,000,000 3 



Color index averages about 0.7. 
White Cells. 



64 



Hayem records 25,000, 19,000, 13,000, 10,000, and 6,000, and 
concludes that the counts vary much not only in different cases, but 
in the same case at short intervals. 

Koblank found 14,700 in a single case. 

Sadler in one case found 6,300 in November and 16,000 in the 
following January; 12,000 in another case; 8,800, 7,700, and 1,916 
in others. 



Table LVIH., A.- 


-Counts 


IN Chronic Nephritis with Uremia. 








White 


Per cent 




Age. 


Sex. 


Red cells. 


ceUs. 


haemo- 
globin. 


Remarks. 


32 


F. 




44,000 




Eclampsia. 


35 






25,000 
9,000 


•• 


Coma first day. 
Clear twelfth day. 


29 


F. 




22,600 






21 




4,680,000 


20,400 






29 






18,900 


80 


Temperature, 102.5'. 


29 


M. 





18,650 




Polynuclear, 83^, 


35 


F. 




18,600 




Coma five weeks after miscarriage. 


35 







18,000 
15,800 




November 21st, arterio-sclerosis. 
November 23d. 






4,184,000 


18,100 


60 


December 2d. 






2,820,000 


16 800 


18 


-Taniiarv 4th. 


18 






17,800 


81 





366 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table LVIII., A.— Counts in Chronic Nephritis with Uremia 
{Continued). 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 








5,236,000 


17,450 


52 


Eclampsia. 




49 


F. 




16,800 








33 






16,300 




Chronic diffuse. 




36 




4,650,000 


16,300 


58 


Polynuclear, 86.7^. 
Lymphocj^tes, 13.3. 
No nucleated reds or deformity. 




25 




3,604,000 


16,200 


50 


Chronic diffuse. 




20 


F. 




15,800 




Differential count normal. 




32 






15,800 


• • 


Chronic diffuse. Eclampsia. 




53 






15,000 
13,200 








38 


M. 




15,000 








45 


M. 




15,000 








35 






14,300 


70 


Chronic diffuse. Died in one month. 


37 


M. 




14,200 








15 


F. 




13,800 








25 


M. 




13,400 








13 




2,360,000 


12,800 


44 


Polynuclear, 77jJ. 
Eosinophiles = 0. 




23 


M. 




12,500 








58 


M. 




12,400 








58 







12,400 


60 






50 


F. 




12,300 








19 




3,104,000 


12.200 


35 


Chronic diffuse. 




59 


M. 




12,100 








9 






11,900 




Interstitial. Asthma. 




63 






11,400 








44 


M. 




11,300 








31 


M. 




11,200 








48 




2,448,000 


9,800 


35 






44 






8,400 


100 






31 




2,500,000 


7,500 


30 






45 


F. 




6,600 








34 


F. 




4,600 








30 


M. 




4,200 









\ 



Chronic Nephritis with Urjemia. 

Summnry. 
White cells. 

Between 2,000 and 6,000 6 

6,000 " 8,000 9 

8,000 " 10,000 11 

10,000 " 12,000 13 

12,000 " 14,000 15 

14,000 " 16,000 12 

16,000 " 18,000 9 

18,000 " 20,000 8 

20,000 or more. 11 

Total .... 94 

Average 15,100 + 



DIFFUSE AND PARENCHYMATOUS NEPHRITIS. 367 

Table LVIII., B. — Chronic Diffuse Nephritis. No Uremia. 



Age. 


Sex. 


White cells. 


Age. 


Se 


s. White cells. 


Age. 


Sex. 


White cells. 


26 


.. 


24,700 


17 


M 


10,400 


28 


M. 


7,600 


55 




23,200 


50 


, 


10,300 


25 


M. 


7,600 


21 




19,000 


43 


F 


10,300 


17 


M. 


7,500 


55 




18,500 


20 




10,200 


55 


M. 


7,400 


51 




18,000 


28 




10,100 


34 


M. 


7,400 


45 


M. 


16,300 


52 




10,000 


50 


F. 


7,300 


11 




16,000 


60 




10,000 


26 




7,300 


66 




15,800 


20 


F 


10,000 


28 


M. 


7,000 


43 


M. 


14,500 


52 


F 


9,800 


42 




7,000 


19 




14,300 


30 




9,500 


41 


ii 


6,800 


56 


F* 


14,000 


25 




9,000 


8 


M. 


6,800 


66 


M. 


14,000 


24 


F 


9,000 


8 


M. 


6,500 


47 




13,100 


36 


. 


8,800 


39 


M. 


6,500 


27 


ii 


13,000 


54 


, 


8,700 


7 


M. 


6,400 


11 


M. 


13,000 


45 




8,300 April 5th 


20 


F. 


6,250 


38 




12,800 April 4tli 
13,900 April 6th 






13,000 
April 9th. 


41 
42 


M. 


5,500 
5,500 






28,650 


30 


M 


8,300 


30 


F.' 


5,200 






April 9th, died. 


27 


F 


8,300 


27 


M. 


5,100 


16 


F. 


12,700 


58 




8,200 


30 


M. 


5,000 


48 




11,200 


16 




8,100 


58 


M. 


4,800 


25 


M. 


11,200 


56 




8,100 


30 


M. 


4,500 


10 


F. 


11,000 


33 


M 


7,900 


41 


M. 


3,000 


47 


F. 


10,800 


14 


M 


7,750 


25 




1,400 


56 


M. 


10,700 


15 


F 


7,700 









The same wide range is seen in Table LVIII., A and B, in which 
I have divided the ursemic and the non-ursemic cases into separate 
tables. It will be seen from these that fifty-five out of ninety-four 
ursemic cases showed leucocytosis, while sixty-one out of ninety- 
two non-ursemic cases showed no leucocytosis. It is impossible to 
suppose that this is mere coincidence. 

Table LIX. — Chronic Diffuse Nephritis. No Uremia. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 


Remarks. 








globin. 




20 




3,492,000 


39,000 


42 


With bronchitis. 


26 


, . 


3,500,000 


26,300 


50 


With acute articular rheumatism. 


36 


. . 


2,560,000 


16,100 


35 


April 14th. 








12,400 


20 


April 30th. 








8,900 




May 1st. 


37 


. . 


3,144,000 


16,000 


40 




11 




3,660,000 


15,600 


52 




33 




3,568,000 


14,600 


45 




22 




4,272,000 


14,400 


45 


Sub-acute. 


19 




5,864,000 


14.300 


65 


Amvloid liver and spleen. Februarv 
12th. 



368 SPECIAL PATHOLOGY OF THE BLOOD. 

Table LIX.— Chronic Diffuse Nephritis; Ko Uraemia {ConUhucfi}. 





1 


White 


Per cent 




Age. Se 


X. Red cells. 


cells. 


haemo- 
globin. 


Remarks. 




6,092,000 


13,700 


.. 


From ear. 




5,740,000 


13,700 




From janger. 


24 . 


3,824,000 
4,268,000 


11,400 
13,600 


55 




16 . 


3,724,000 


11,300 


45 




35 .. 


3,164,000 


10,600 


50 


Tertiary syphilis. 


42 . 


4,228,000 


10,100 


65 


(Edema. 


19 . 


3,776,000 


10,000 


56 


Cardiac hypertrophy. 


28 . 


4,560,000 


10,000 


45 




47 . 


i 4,450,000 


9,800 


50 




21 .. 


4,080,000 


8,600 


70 




42 .. 


3,416,000 


7,000 


55 




55 . 


4,360,000 


6,300 


50 


Ascites. 


24 . 


4,800,000 


5,700 


65 




26 . 


1,468,000 


3,800 


23 


Polynuclear, 70^; lymphocytes, 23j^; 
large lymphocytes, 4. 4^ ; eosinophiles, 
2.6^; reds, megaloblasts, 3; normo- 
blasts, 2; microblasts, 1. Consider- 
able variation in size; many oval 
forms; considerable poikilocytosis. 




1,136,000 




19 


Polynuclears, 71. 8j^; lymphocytes, 24. 2j?; 
large lymphocytes, 2. 2^; eosinophiles, 
1.2;^; myelocytes, 6; megaloblasts, 6; 
normoblasts, 3. November 5th. 




1,752,000 




22 


Polynuclears, 69.4^; lymphocytes, 
25.2,';; large lymphocytes, 3.8^,^ eo- 
sinophiles, 1.6,'^; megaloblasts, 4; 
normoblasts, 2. November 13th. 




2,248,000 




30 


Polynuclears, 65.4^; lymphocytes, 28,^; 
large lymphocytes, 3,'^; eosinophiles, 
3.4;^; basophiles, 2; megaloblasts, 1; 
normoblasts, 0. November 20th. 




2,540,000 




48 


Polynuclears, 70. 2^;; lymphocytes, 23,^ ; 
large lymphocytes, 2. 65; ; eosinophiles, 
^A'fc ; basophiles, . 8^. Red variation in 
size and shape less marked. Megalo- 
blasts, 1. November 27th. 




3,392,000 




60 


December 6th. 




3,580,000 


5,866 


65 


Polynuclears, 79^; lymphocytes, 17.6c : 
large lymphocytes, 1.8^; eosinophiles. 
\.Q</c. Reds stain weU; slight poiki- 
locytosis and variation in size; no 
nucleated reds. 


36 .. 


5,060,000 




75 


Hemorrhagic nephritis. 



Chronic Diffuse Nephritis; No Ur.smia. 
White cells. 

Between 2,000 and 6,000 4 

" 6,000 " 8,000 .12 

8,000 " 10,000 18 

" 10.000 " 12,000 27 

12,000 " 14,000 11 



CHRONIC INTERSTIAL NEPHRITIS. 369 

Between 14,000 and 16,000 9 

16,000 " 18,000 5 

20,000 + or more 6 

Total 92 

Average 11,600 + 

CHRONIC INTERSTITIAL NEPHRITIS. 

Hayem found the fibrin more increased in this form of nephritis 
than in any other, and the anaemia less pronounced. 
Grawitz distinguishes two stages : 

I. As long as the heart is strong enough to overcome the in- 
creased resistance at the periphery and the disturbances of circula- 
tion are not marked, the blood is normal. 

II. When compensatory hypertrophy is no longer sufficient to 
do the work of forcing the blood through the system, the usual 
effects of failing compensation (see Heart Disease, page 353) appear 
(dilution and subsequent concentration of the blood). 

The white cells are normal. 

Pieraccini {lor. clt.) has recently studied with care seventeen 
cases of nephritis of various types, paying especial attention to the 
differential count of leucocytes. He concludes (page 282) that: 
"' Toxsemia of renal origin, occurring in any variety of nephritis, 
diminishes the number of circulating eosinophiles in proportion to the 
degree of the toxaemia. In the severest cases the eosinophiles al- 
together disappear from the circulation. . . . With the remission 
of toxic symptoms the eosinophiles tend to return to normal or to 
rise above normal." The disappearance of eosinophiles from the 
blood of a case of nephritis is therefore, he says, a bad prognostic 
sign. This is of special importance in the nephritis of pregnancy. 

In conditions resembling those of uraemia — e.g., hysterical, epi- 
leptic, or syphilitic convulsions, coma from alcoholism, apoplexy or 
following epilepsy, cardiac asthma or cardiac oedema — Pieraccini 
finds the eosinophilic cells undiminished. [He does not refer to the 
type of convulsions occurring in dementia paralytica and other types 
of insanity in some of which Capps and Burrows found marked dimi- 
nution or absence of eosinophiles (see page 389), but it is very pos- 
sible that these convulsions were also of toxic, if not of ursemic origin.] 

Pieraccini considers the percentage of eosinophiles a valuable 
datum in the diagnosis between bronchial asthma and renal asthma. 
In the latter there is a diminution, in tlie former an increase of eosin- 
ophiles. Between a "cavdio-renal " inula " reno-cardial " dropsy 
24 



370 



SPECIAL PATHOLOGY OF THE BLOOD. 



he considers the presence of eosinophiles in normal or increased per- 
centage to mean that the heart and not the kidney is chiefly to blame. 

The reappearance of eosinophiles, however, does not seem to him 
to better the prognosis as much in uraemic states as it appears to in 
infectious diseases (Tllrck). Especially in chronic uraemia the sys- 
tem seems to become so adjusted to its burden that the eosinophiles 
may reappear and remain in the circulation despite decided symp- 
toms of systemic poisoning {loc. clt., p. 193). 

In other respects Pieraccini finds no abnormalities in the blood 
of cases of nephritis. The number and quality of erythrocytes, leu- 
cocytes, and platelets are normal. Kouleaux formation, coagulation, 
and the size and staining reaction of the corpuscles are also normal. 

Table LX. — Chronic Interstitial Nephritis. 



No. 


Age. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


1 


29 




23,700 


65 




2 


26 




19,700 


70 


Death. 


8 


39 


6,040,300 


19.000 


80 


Coma; moribuDd. 


4 


31 




17,200 


70 


March 25th. 








15,400 


65 


Marcli 30th. 


5 


56 




16,200 


95 




6 




4,548,000 


15,000 


50 




7 


58 




14,500 


75 


Ur?eraia. 


8 


35 




14,400 


85 


Umemia. 


9 


40 




14,100 


60 


Chronic gastritis. 


10 


23 




18.600 


65 


Uraemia. Autopsy. 


11 


36 




13,600 


72 


Uraemia. 


12 


50 




12,800 


65 


Death. 


18 


47 




12,600 


70 


Retinitis. 


14 


26 




12,400 


90 




15 


51 





12,300 


80 


Mitral sufficiency. 


16 


50 




12,200 


90 


Mitral sufficiency. 


17 




4,240,000 


12,000 


67 




18 


22 




11,600 


65 




19 


64 




11,200 


75 




20 


22 


5,626,000 


11,100 


50 




21 


23 




10,800 






22 


40 


3,150,000 


9,800 


80 




28 


46 




9,700 




Uremia: moribund. 


24 


69 




8,500 


87 




25 


34 


3,536,000 


8,300 


57 




26 


47 




8.200 


80 




27 


60 




7,800 


95 


Cerebral hemorrhage. 


28 


46 




7,300 






29 


52 




6,800 


80 


Uraemia. 


80 


52 




6,800 


65 


Urasmia. 


81 


20 


4,088,000 


6,000 


52 




82 


82 




6,000 


65 




88 


60 




5,900 






84 


36 




5,400 


60 





STOXE IN THE KIDNEY. 



371 



PYELONEPHRITIS. 

Table LXI. speaks for itself. The ancemia is often severe and 
leucocytosis is the rule in my experience, but Pieraccini reports 
Qoc. cit., p. 252) four cases of "open pyelonephritis" with or with- 
out cystitis, none of which showed any leucocytosis nor any change 
in the percentage of the different leucocytes. 



Table LXI. — Pyelonephritis. 



1 


Age. 


Sex. 


Red cells. 


White 

cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 
3 
4 

5 


24 

26 
33 
26 
40 


F. 

F. 
M. 
F. 


3,056,000 
2,976,000 
2,696,000 
3,272,000 
4,200,000 
4,536,000 
2,356,000 


21,200 
15,200 

18,800 
25,200 
16,800 
15,550 

7,280 
6,800 


41 
38 
33 
33 

36 
65 


March 10th. Uraemia, 
March 13th. • 
March 27th. 
April 14th. 

Perinephritic abscess too. 
Cystitis also. 
Cystitis also. 
PyeHtis. 



Table LXII. — Cystic Kidney. 



c 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


55 


M. 


3,664,000 


4,400 




Polynuclear cells, 72 per cent. 
Supposed cancer. Enormous firm 
tumor on each side. Autopsy. 



The cases recorded in Table LX. are probably not inconsistent 
with these rules. Of the seven cases with leucocytosis three were 
uraemic, and in a fourth the influence of digestion is seen. The 
haemoglobin is lower than we should expect from Grawitz's account. 

Uroemia, it would appear from these tables, may cause leucocy- 
tosis, or at any rate is not infrequently associated with it. Aside 
from uraemia and hemorrhage, nephritis probably does not cause 
leucocytosis. 

STOXE IX THE KIDXEY. 

(See Table LXIII.) The state of the blood depends on the 
amount of ulceration caused by the stone; when this is considerable 
we have leucocytosis. 



dT2 SPECIAL PATHOLOGY OF THE BLOOD. 

Table LXIII.— Stoxe rx the Kidney. 





Age. 


Sex. 


z 






1 






2 


51 




3 


55 




4 


19 


M. 


5 




M. 


6 


53 




7 


20 




8 


25 


F. 


9 
10 


48 
24 


M. 


11 


58 


M. 


12 


23 




13 


52 


M. 


14 


45 


M. 


15 


51 


M. 


16 


36 




17 


24 




18 


30 


M. 


19 







Red cells. 



White 
cells. 



Per cent 
hseino- 
globiu. 



llHniark> 



4,350,000 
4,'l6(),00b 
5*68(),"obb 

3,0^" boo 



4,340.000 
6,100,000 



800 
200 
500 
800 
600 
200 
750 
900 
200 
000 
990 
600 
000 
800 
500 
500 
000 
300 
300 
980 
000 
500 



Temler in loin. 

August lOth. 

August 12th. Pain gone. 

Much pus in urine. 



73 
65 

85 

85 
30 
95 
95 

88 
70 
85 



Haematnria. 
Uric-acid stone passed. 



Much pus in urine. 
Two weeks later. 



as 



Dlar/iiostir Vf/t/r. 

Cancer would also cause leucocytosis, Init would not increase fibrin 
a rule, while most cases of stone Avitli ulceration do increase fibrin. 

FLOATING KIDNEY. 
Tlie blood is normal. This fact has some diagnostic value; for 
example, when we confound appendicitis with floating kidney, as 
has been done (see page 260). The presence of leiicocytosis ex- 
cludes the latter and favors the former. Most tumors or abscesses 
with which a floating kidney might be confused could be distin- 
guished by the same criterion. 

Table LXIV.— Floatixg Kidxey. 













Per cent 




^• 


Age. 


Sex. 


Red ceUs. 


White cells. 


h£emo- 


Remarks, 


•Zi 










globin. 




1 


47 




4,650,000 


23,000 
17.400 


45 


March 28th. Peritoneal inflamma- 
tion. 
April 4th. 






' 


21.300 




April 9th. 








21.800 




April 15th. Diff. count 300. Polv- 














nuclear, 87 per cent : small Ivm- 












phocvtes. 7; large lymphocvtes. 












5.5; eosinophiles, .5; reds aver- 














age size ; very few poikilocy tes. 



BRONCHITIS. 
Table LXIV.— Floating Kidney {Continued). 



373 













Per cent 




_• 


Age. 


sex. 


Red cells. 


White cells. 


haemo- 


Remarks. 


55 










globin. 




2 


65 




4,432,000 


11,800 


65 


Double. 


3 


24 






11.200 


70 




4 


37 


F. 


5,056,000 


9,200 


75 




5 


41 


F. 


4,684,000 


9,000 


75 




6 


24 


F. 




8,100 






7 


67 


F. 




8,000 


65 




8 


23 


F. 


5,400,000 


6,000 


69 




9 


43 


F. 


4,700,000 


2,400 


76 




10 


38 
24 

38 


F. 
F. 
F. 






75 

80 
67 


Aneurism of arch also. 


11 








12 


4,416,000 


5,800 




13 


24 


F. 




7,600 


80 





A large number of similar counts might be quoted. 

HYDROXEPHROfelS. 
Table LXV. — Hydronephrosis. 



-i 


Age. 


Sex. 


z 






1 


52 




2 


4 




3 


24 




4 


85 


•■ 



Red cells. 



4,016,000 
5,496,000 
5,140,000 



White 


Per cent 




haemo- 




globin. 


16,400 


75 


10,800 




14.300 


60 


28,600 




9,200 


80 


6,500 


85 



Remarks. 



March 7th. 
March 12th. 

Operation. Congenital. 
Intermittent. 



PYOXEPHROSIS. 

Case I. — Female, 36; leucocytes, 16,200, of which 85 per cent 
are neutrophiles. Half a pint of pus found at opera tioji. 

Case II.— July 25th— Eed cells, 3,856,000; white cells, 9,800; 
haemoglobin, 45 per cent. July 9th — Red cells, 3,450,000; white 
cells, 9,000; haemoglobin, 55 per cent. August 3d — White cells^ 
6,650. August 6th — Operation. Pint of foul pus. Death. 



DISEASES OF THE LUNGS. 

BRONCHITIS. 

" Acute catarrhal and chronic purulent bronchitis have relativelj 
little leucocytosis in most cases " (v. Limbeck). 

Except for this and a few other passing references, there is 
hardly anything in literature on the blood in bronchitis, so that I 



374 



SPECIAL PATHOLOGY OF THE BLOOD. 



shall be forced to base my statements chiefly on the few counts re- 
corded at the Massachusetts General Hospital. 

ACUTE BRONCHITIS. 

Aside from "capillary bronchitis," cases are not infrequently 
seen in which the signs are simply those of general bronchitis of 
the liner tubes, yet the symptoms are much more like pneumonia. 
Whatever may be the real conditions in the lungs of such pa- 
tients, their blood is not infrequently exactly like that of pneumonia 
and does not help at all in the differential diagnosis between the 
two diseases (see Cases 1 and 2, Table LXVL). 
Table LX VI.— Acute Bkonchitis. 











Per cent 




Age. 


Sex. 


Red cells. 


White cells. 


haemo- 


Remarks. 










globin. 




75 


■• 


5,808,000 


45.000 
26,400 
6H. SOO 


58 


Fourth day. 
Eleventh day ; died. 


70 


F. 


4,420,000 


41.000 


70 




56 


F. 


4,800,000 


26.(100 


65 


Temperatin-e, 103°. 


6 






26.000 




AVlioopiug cough. 


28 






25,900 
17.100 


67 


Temperature, 101°. 
Fourth (lay ; well. 


S2 






25.750 




Subacute; temperature, 99°. 


34 







23.500 


80 


With enteritis : temperature, 103°. 


22 


M. 





23.450 


67 


Temperature, 101°. 


21 






22,200 




Temperature, 101'. 


7 






21.200 




Temperature, 103°. 


58 






20.400 






44 




5,660,000 


20.100 


58 


Temperature. 103"'; asthma. 


31 







19,100 




Temperature. 100°. 


3 






19,000 




Temperature, 99.5°. 


36 







19,000 




Temperature, 98°. 


50 






17.200 • 


62 


Subacute. 


42 


•• 





17,000 
15,000 




First day ; temperature, 100°. 
Four days later, temperature, 98°c 


■ 38 






15,100 




Temperature, 103 . 


41 


F. 


4,'l92,00b 


15,000 
11.300 
17.600 


65 


November 5th. 
November 16th. 
November 25th. 


55 






15,000 




Subacute; temperature, 100°. 


26 


M. 


.... 


14.200 


70 


Temperature, 101.5". 


22 






13,800 
16,300 
16,400 


60 


Temperature, 102°. 
Third day. 
Sixth da3^ 


55 






13,000 


, . 


Temperature, 100°. 


5 






13,000 

12,600 

11,300 

6,600 




Temperature, 102.5°. 
Third daj'; temperature, 101° 
Sixth day; temperature, 100°. 
Eleventh day ; temperature, 98°. 


23 







12,600 




Temperature, 101.5 = 


30 






12,000 


65 


Temperature, 102°. 


28 


F. 


6,'l96,00b 


12,000 







ACUTE BRONCHITIS. 
Table LXVI.— Acute Bronchitis {Continued). 



375 



Age. 


Sex. 


46 


M. 


13 




20 


M. 


40 


M. 


31 




69 




42 


M. 


50 


F. 


50 


M. 


38 




48 




25 




52 


M. 


25 


M. 


56 


F. 


36 


M. 


43 




29 


M. 



Red cells. 





Per cent 


White cells. 


haemo- 




globin. 


11,800 


.. 


10,800 




10,600 


65 


10,300 




10,200 




9,400 




9,800 




8,000 


72 


7,900 


50 


7,800 




7,800 




7,200 




7,000 


70 


7,000 


74 


6,800 




6,000 


72 


8,600 




5.900 




4,000 


80 



Remarks. 



5,260,000 
5,952,000 



4,892,000 



Temperature, 104°. 
Temperature, 102°. 
Temperature, 104°. 
Temperature, 101°. 
Temperature, 102°. 
Temperature, 101°. 



Temperature, 99°. 
Temperature, 102°. 
Temperature, 100'. 

Temperature, 103*. 

October 31st. 
iSTovember 3d. 
Temperature, 100°. 
Temperature, 102°. 



Acute and Subacute Bronchitis. 
White cells. 

Between 2,000 and 6,000 13 

6,000 " 8,000 31 

8,000 " 10,000 18 

10,000 " 12,000 23 

12,000 " 14,000 17 

14,000 " 16,000 15 

16,000 " 18,000 10 

18,000 " 20,000 13 

20,000 " 22,000 8 

22,000 " 24,000 7 

24,000 " 26,000 7 

26,000 " 45,000 7 

Total 168 

Average 12,800 + 

Table LXYII. — Chronic Bronchitis. 



Remarks. 











White 


Per cent 


1 


Age. 


Sex. 


Red cells. 


cells. 


haemo- 
globin. 


1 


51 






88,000 




2 


82 






80,400 


80 


3 


24 






29,500 




4 


Adult 


ii. 


3,680,000 


18,500 


63 


5 


52 






18,400 


90 



376 SPECIAL PATHOLOGY OF THE BLOOD, 

Table LXVII. — Chronic Bronchitis (Co/itinued] 



Age. 



42 
34 

68 
35 

48 

64 
62 
65 
68 
43 

60 
36 

74 
27 

61 
20 

18 

26 
45 
29 
20 



Sex. 



M. 



F. 

M. 
F. 
M. 



Red cells. 



5,384,000 
4,300,000 

4,700,000 

4," 100, boo 



White 
cells. 



17,100 
16,600 
16,400 
15,400 
15,000 

15,000 
14,300 
12,900 
12,400 
11,000 

10,500 

10,100 

8,900 

8,800 

8,000 
7,925 
7,792 

6,700 
6,700 
5,500 
5,062 



Per cent 
haemo- 
globin. 



70 
70 

80 



85 



63 

78 



70 
62 
61 



Remarks. 



With emphysema. 

Chronic febrile, with laryngitis. 

Recovery. 
Temp. 98. 6 \ 

Temp. 100' ; with asthma. 
Fibrinous. 

Temp. 98^ ; chronic with emphy- 
sema. 



Temp. 98°. 

Constipation ; neurasthenia ; 

weeks afebrile. 
Five months. 

Keratitis, conjunctivitis. 

symptoms. 
Asthma. 

Empyema of the antrum. 
One month. 



two 



In the majority of acute cases, however, the blood shows no 
changes unless concentration due to cyanosis be present. 

In chronic cases (Table LXVII,) leucocytosis is uncommon; 
more so, I think, than the table I'epresents. If more counts were 
added, nearly all, I think, would be normal. 

The red cells and haemoglobin show no changes to speak of in 
either acute or chronic cases. 

The blood has no diagnostic value so far as I know, except that 
when pneumonia is in question a normal count of white cells speaks 
against it and in favor of bronchitis. If emphysema is also present, 
it sometimes produces a condition of the blood different from that 
in simple bronchitis. 

EMPHYSEMA AND ASTHMA, 

Grawitz reports an increase in the number of red cells in e??^- 

physema, which he believes to be due to cyanosis, and this covers 

up the really anaemic condition of the blood of many patients. 

Practically the same conditions are present as in the cyanosis of 



EMPHYSEMA AND ASTHMA. 



377 



heart disease (see page 353) and the concentration of the blood is 
brought about in the same way. Leichtenstern ' noticed a diminu- 
tion in haemoglobin at the time when the heart first fails, due proba- 
bly to the diminished blood pressure which allows the lymph from 
neighboring tissues to flow into the vessels and dilute the blood. 

In both asthma and emphysema it has been noted by Miiller,' 
Gollasch/ Gabritschewsky * and others that eosinophiles are very 
numerous in the sputum, and Fink^ also noted an increase of the 
same cells in the blood, running as high as 14.6 per cent instead of 
the normal one to two per cent. This increase is present only at 
the time of the paroxysm and for a short time before and after it. 
Von Noorden found in one case 25 per cent of eosinophiles during 
an attack, and a few days later could discover but one eosinophile 
in twelve cover slips. In another case, after five attacks on suc- 
cessive days, the eosinophiles were 33 per cent. Billings ^ reports 
the following counts : 



January 26th. 



February 4th. 



February 11th. 



Red cells 

White cells 

Haemoglobin 

Polymorpho nuclear 

cells 

Lymphocytes (small). . 
Lymphocytes (large). . 
Eosinophiles 



3,911,000 
8,300 
68.0 per cent. 

36.0 per cent. 

5.0 per cent. 

5.2 per cent. 

53.6! per cent. 

Few normoblasts. 



4,221,000 
7,500 
75 per cent. 



38.2 per cent. 



4,630,000 
7,600 
86 per cent. 



33. 9 per cent. 
No nucleated red 
cells. 



Their presence in increased numbers before a paroxysm is said 
to make it possible to predict ' its coming (v. ]S"oorden, Schwer- 
skewski). Coler reports a case of asthma with leucocytosis of 52, ~ 
000, 25 per cent of which was made up of eosinophiles. The case 
was complicated with extensive purpura, painful muscles, and ex- 
treme cyanosis, but microscopic examination of the affected muscles 
showed no trichinae. 

Wolff " followed a case for over a year and found the eosinophiles 

^ "Ueber das Hb-Gehalt des Blutes," etc., Leipsic, 1878. 

^Ref. in Fink, "Beitrage z. Kennt. des Eiters," Dissert., Bonn, 1890. 

3 Fortschritte der Med., 1889. 

^ Arch. f. exp. Path, und Pharm., 1890, p. 83. 

^ New York Med. Journal, May 22d, 1897. 

^ Wolff: Ziegler's Beitrage, vol. xxviii. 



378 SPECIAL PATHOLOGY OF THE BLOOD. 

always over ten per cent, although during six months of this time 
there were no paroxysms. He has noted similar conditions in two 
cases of hay fever. 

I have watched one subacute case without well-marked parox- 
ysms or periods of perfect healtli. The blood was frequently ex- 
amined and showed always a slight leucocytosis with eleven to fif- 
teen per cent of eosinophiles. As this applies only to pure hronchuil 
asthma and not to cases secondary to disease of the heart or kidney, 
Schreiber states that we are enabled to distinguish bronchial from 
cardiac or renal asthma by the increase of eosinophiles in the blood 
and sputa in bronchial cases, which does not occur in asthma due to 
cardiac and renal trouble. Pieraccini confirms this. Other records 
are (Gabritschewsky) : 

Case I.— White cells 8,200 

Eosinophiles 10.08 per cent. 

Case 11. -White cells 6,800 

Eosinophiles 22.4 per cent. 

Polynuclears 35 

Table LXIX, — Asthma. 











White 


Per cent 




• 


ARe. 


Sex. 


Red cells. 


cells 


haemo- 


Remarks. 


^2; 










globin. 




1 


55 






39,000 
55,000 


90 


Bronchial asthma; bronchopneu- 
monia. 

February 2d. Diff . count 200 cells : 
Polynuclear, 88 per cent; small 
lymphocytes, 3; large lympho- 
cytes, 9; eosinophiles, 0. 

February 5th. 










33,000 






Februarv 7th 










30,000 






February 9th. 










20,000 






February 12th. 










21,000 






Februarv 14th. 










18,000 






February 17th. 










19,000 






February 26th. 


2 


26 


M. 




32.500 






Fifth. Temp. 100\ Bronchitis 














and emphvsema. 










19.200 




Seventh. Temperature normal. 


3 


45 






32,000 

28,000 
30,000 
28,000 


85 


March 16th. Emphysema; pneu- 

mococcus; bronchitis. 
March 19th. 
March 22d. 
March 30th. 


4 


33 




...<.... 


31,500 
39,000 


85 


Julv 17th; influenza. 
July 23d. 


5 


50 






28,000 


75 


Emphysema ; bronchitis : mitral iu- 














1 


sufficiencv. 



SYPHILIS OF THE LUNG. 
Table LXIX. — Asthma {Continued). 



379 









' White 


Per cent 






Apre. 


Sex. 


Red cells. S.^ 


haemo- 


Remarks. 


z 










globin. 




6 


31 






21,000 


95 


Bronchial with unresolved pneu- 
monia. Diff. count 500 cells: 
Polynuclear, 71.4 per cent; lym- 
phocytes, 24.8; eosinophiles, 3.8. 


7 


29 






20,000 


67 


Bronchial. 


8 


50 


F. 




19,800 


50 


Typical bronchial asthma during 
paroxysm. 


9 


29 






18,600 


85 


Diff. count: Polynuclear, 57.3 per 
cent; lymphocytes, 28.9; eosino- 
philes, 13.8. 


10 


55 






16,400 


90 




11 


78 






16,000 

13,800 


65 


February 14th. 
February 16th. Death. 


12 


27 






15,400 


90 


Mitral insufficiency. 


13 


32 






14,300 


72 


Bronchial. 


14 


44 






14,200 


95 


Nasal ; chronic ethmoiditis. . 


15 


36 




1 13,800 


85 


Bronchial. 


16 


38 




1 13,600 


80 




17 


30 




! 13,600 


85 


Bronchial. 


18 44 




: 13,600 


87 


Bronchial. 


191 60 




i 13,300 


85 


Bronchial. 


20| 70 


M. 


5,500,000 13,000 




Chronic with emphysema. 


211 25 




1 12,400 


90 


Bronchial. Diff. count 500 cells: 












Polynuclear, 64 per cent; lym- 


1 










phocytes, 27; eosinophiles, 9. 


221 24 






12,000 


75 


Eosinophiles, 4 per cent. 


23i 35 






10,860 


65 


Bronchial. Diff. count 500 cells: 
Polynuclear, 75.6 percent; lym- 
phocytes, 16.6; eosinophiles, 7.8. 


24; 68 






10,000 


85 




25| 29 


M. 




9,750 






26; 58 






9,400 


85 




27' 35 

i 






8,000 


90 


Bronchitis ; emphysema Diff. 
count 400 cells: Polynuclear, 60 
percent; lymphocytes, 30; eosin- 
ophiles, 10. 


28, 29 






8,000 


80 


Emphysema. 


29] 62 







7,400 


80 


Chronic interstitial nephritis. 


30! 25 







6,600 


85 


Arteriosclerosis. 



For Pneumonia, see page 189. 

For Phthisis, see page 291. 

For Abscess of Lang, see page 380. 

SYPHILIS OF THE LUNG. 

In a case of syphilitic infiltration of the king (autopsy — Drs. 
Councilman and Wright) recently observed at the Massachusetts 
General Hospital the leucocytes rose rapidly from 8,700 to 27,400 
as deatli approached. 



380 SPECIAL PATHOLOGY OF THE BLOOD. 

Table LXX. — Gangrene of Luxg and Abscess. 



No. 


Age. 


Red cells. 


White cells. 


Per cent 
hseraoglobin. 


Reruarks. 


1 


49 




39,900 




Abscess; autopsy. 


2 


42 




22,400 




Abscess after grippe. 


B 


19 




18,400 




Gangrene. 


4 


48 


4,712,666 


16,600 

7,400 

20,000 

11,900 


65 


November 7tb; abscess. 
November 9tb. 
November 14th. 
November 16th. 


5 


48 




16,400 




Abscess after immersion. 


6 


54 




15,300 
20,500 
18,300 
23,000 
27,000 
27,000 
31,000 
17,000 
20,000 
15,800 




First day; gangrene. 
Fourteenth day. 
Sixteenth day. 
Nineteenth day. 
Twenty-first day. 
Twenty -sixth day. 
Twenty -ninth day. 
Thirty-second daj^ ; better. 
Thirty-sixth day. 
Fifty-fourth day. 


7 


50 





9,600 




Gangrene. 


8 


29 





8,400 


80 


Abscess. 



1 



PART V. 

DISEASES OF THE NERVOUS SYSTEM, CON- 
STITUTIONAL DISEASES, AND HEMOR- 
RHAGIC DISEASES. 



CHAPTER VIII. 

DISEASES OF THE XERVOUS SYSTEM. 

NEURITIS. 

Ix cases of multiple neuritis, febrile and apparently of an infec- 
tious nature, the following counts are found in the records of the 
Massachusetts General Hospital : 









White 


Per cent 




o 


Age. 


Sex. 


Red ceUs. 


cells. 


hsemo- 


Remarks. 


2; 










globin. 




1 






4,816,000 


25,000 
24,800 
18,700 
21,000 


42 


July 10th. Temperature 101 \ 
July 13th. 
July 16th. 
July 20th. 








4,320,000 


16,000 


60 


July 25th. 






1 


28,700 




July 31st. No fever. 






1 


19,500 




August 7th. No fever. 










23,200 


. . 


August 20th. No fever. 


2 


24 






22,800 


70 




3 


41 








10,900 


85 


Brachial. 


4! 37 






. . 


10,400 


85 




5| 42 








10.800 


68 


Traumatic. 


6! 32 

71 49 








10,100 


85 










9,600 


61 




8 


24 








8,400 


. . 


Polynuclear, 36 per cent ; lympho- 














cvtes, 62;eosmophiles. 2, (Count, 














300 cells.) 


9i 22 






6,400 















The first case, a boy of eleven, recovered and left the hospital 
well. 



382 



SPECIAL PATHOLOGY OF THE BLOOD. 



But these changes occur also in alcoholic (afebrile) neuritis, as 
the foUowincr counts show : 



6 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 
2 

3 
4 


27 
40 

39 
25 


_ 


3.608.00b 
3.260,000 

3,584,000 


20,800 
21,300 
11,400 
16,100 
15,000 
14,000 
13,700 
12,000 
11,200 
7,700 
7,600 
:6,700 


90 

75 
64 
60 
45 

68 

80 

82 


January 31st. 
February 3d. 
February 4tb. 
Pneumonia. No autopsy. 



In all cases the counts were made just at meal-tinie, so that the 
leucocytosis is not due to digestion. Gastritis was not present in 
either case. 

One case of post-diphtheritic neuritis in a chihl of eight showed 
the presence of anaemia only: Red cells, o, 850, 000; white cells, 
7,393; hsemoglobin, 70 per cent. 

Neuritis in lead poisoning does not affect the count of leuco- 
cytes, as twenty-five cases studied at the Massachusetts General 
Hospital have shown. 

Table LXXL — Herpes Zoster, 



No. 


Age. 
52 


1 


2 


46 


3 


34 


4 


74 


5 


53 


6 


65 



Red ceUs. 



White cells. 



15,500 

14,000 

14,200 

15,000 

10,000 

9,100 

8,500 

5,700 



Per cent 
h£emoglobiu. 



90 



90 

60 
90 



Remarks. 



Temperature 
October 23d. 
October 25th. 
October 28th. 



Neuralgia, whether facial, intercostal, sciatic, or ovarian, showed 
normal blood in numerous cases examined at the Massachusetts 
General Hospital. 



DISEASES OF THE BRAIN. 



383 



DISEASES OF THE BRAIX. 

Menmgitis (see Inflammation of Serous Membranes, page 284). 

Zappert in one case of b^^ain abscess found only 4,000 white cells. 

In pachymeningitis liannovrhagica and cerebral syphilis (one case 
of each) v. Jaksch found leucocytosis My own experience has 
been the same. 

EPILEPSY. 
Pieraccini (loc, cit.) records the following: 



6 
2; 


Age. 


Per cent 
polynuclear. 


Per cent 
lymphocytes. 


Per cent 
eosinophiles. 


Remarks. 


1 
2 


17 
24 


74.3 
90.3 


18.1 

8.3 


7.4 
1.2 


During post-convulsive sleep. Pa- 
tient is an idiot. 
Two hours after convulsion. 



Table LXXII. — Puerperal Eclampsia (Pieraccini). 



No. 


Per cent 
polynuclear. 


Per cent 
lymphocytes. 


Per cent 
eosinophiles. 


Remarks. 


1 


73.7 




0.2 


Uraemic. 




78.2 





5.3 


0. K. 


2 


87.1 
'82.9 






1.2 


Eclamptic. 
0. K. 




77.3 




2.5 


0. K. 


3 


84.6 
79.6 






2.6 


Eclamptic. 
0. K. 




84.0 




7.2 


0. K. 


4 


80.3 

77.4 





1.2 
2.5 


Eclamptic. 
O.K. 



Cerebral and Cerebellar Tumors. — Von Jaksch found slight 
leucocytosis in two cases of brain tumor and one of cysticercosis. 
Zappert found normal blood in oue case of cerebral tumor. 

Table LXXIIL— Cerebral Tumor. 



o 


Age. 


Sex. 


^5 






1 


43 




2 38 




3 10 




4 


59 





Red cells. 



White 


Per cent 


cells. 


haemo- 




globin. 


18,100 


70 


16,900 


75 


16,200 


90 


16,200 


80 


15,900 





Remarks. 



April 7th. 
April 9th. 



384 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table LXXIII.— Cerebral Tumor {Continued). 



— 








White 


Per cent 




Age. 


Sex. 


Red cells. 


cells. 


haei 


no- Remarks. 


z 










glo 


3in. 










17,000 




April 11th. 










17,900 




April 14tli. 


5 


25 







16,000 


10 





6 


11 






15,000 

21,600 
12,600 
24,500 
29,900 
14,400 
19,600 
18,100 
19,000 
31,000 
25,200 
26,400 
21,000 
31.400 
25,500 
26,600 
30,800 
21,000 
29,200 
24,000 
19,400 
17,200 
12,000 
13,800 


8 
8 


April 10th. Glioma of the corpora 
quadrigcmina and cerebellum. 
Autopsv. 

April 20th. 

April 21st. 
June 80th. 

July 18tii. 

July 28(1. 

July 27th. 

July 29th. 

August 2d. 

August 5th. 

August 10th. 

August 12th. 
1 August 16th. 

Augu.st 19th. 

August 21st. 

August 28d. 

August 25th. 

August 29th. 

September 2d. 
i September 6th. 

September 8th. 

September 10th. 

September 12th. 

September 18th. Died October 12th. 


7 


22 






15,000 






8 


13 






14,500 
13,700 






9 


9 






14,400 


8 


5 Died. 


10 


43 






14,000 


10 





11 


? 






13,100 


8 


5 


12 


26 






12,500 






13 


4 






12,200 


7 





14 


27 






10,600 


6 





15 


42 






10,400 


8 





16 


32 






9,840 


7 





17 


28 






9,600 


6 


8 


18 


25 






9,000 


9 





19 


83 






9,000 


7 


2 


20 


48 






8,200 


9 





21 


24 






7,800 


9 





22 


52 






7,000 






28 


60 






5,800 


9 


5 


24 


31 

1 


4,100 







Fresh cerebral hemorrhage usually causes leucocytosis, as the 
followino^ table shows : 



DISEASES OF THE BRAIN. 385 

Table LXXIV. — Cerebral Hemorrhage. 



1 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


42 


M. 




31,000 


95 


Autopsy. 


2 


52 


M. 




30,000 




Polynuclear cells, 92 per cent. 








5,512,000 


25,000 


85 


Autopsy. 


3 


62 






30,000 


100 


Autopsy. 


4 


60 






29,700 




Autopsy. 


5 


57 






27,000 


100 


Autopsy, ventricular. 


6 


19 






24,000 


80 


Cerebrospinal, disseminated. 
Death. 


7 


60 






23,600 
26,000 




Second day. 


8 


55 







22,200 




Coma. 


9 


69 







19,800 






10 


65 


.. 





19,800 


78 


Autopsy. 


11 


47 


M. 





19,400 




Autopsy. 


12 


54 






19,000 


65 




13 


75 






18,800 
22,600 
16,300 


88 


November 17tli. 
November 19th. 
November 21st. Autopsy. 


14 


? 







18,400 


80 


Multiple with rneningeal hemor- 
rhage. Autopsy. 


15 


47 






18,400 


85 


Chronic diffuse nephritis. 


16 


43 






18,000 


85 


Hemiplegia. 


17 


63 






17,400 


95 


Death. 


18 


56 







17,400 


100 


Coma. Hemiplegia. 


19 


49 


. 





17,200 


95 




20 


70 


F. 


5,560,000 


16,800 
15,600 


68 
90 


Hemorrhage four days before 
count. Autopsy. 


21 


70 







16,700 


85 


Death. 


22 


50 






16,300 


94 


March 20th. Right hemiplegia 
in aphasia. 


23 


59 






16,000 






24 


58 






13,800 
15,700 


80 


March 21st. 
Death. 


25 


2 






15,000 


90 


Death. 


26 


62 






14,900 




Temp, 104.7°. Died. 


27 


50 






14,500 


78 


Aphasia. 


28 


58 







14,000 


90 




29 


48 






13,800 


90 


Aphasia. 


30 


52 






13,800 




Hemiplegia. Died. 


31 


53 


.. 




13,000 


100 


Death. 


32 


48 






13,000 




Hemiplegia. Coma. 


33 


51 






12,600 


95 




34 


9 






12,400 


95 


Death. 


35 


37 


M. 




12,300 


70 




36 


68 






12,000 
11,900 




No coma. 


37 


55 






11,800 






38 


42 






11,600 




' 


39 


56 






11,200 


100 


Death. 


40 


48 






10,800 


70 




41 


49 






10,500 


90 


Nephritis. Death. 


42 


38 


M. 




10,400 


58 


Conscious ; recovered. 



25 



386 SPECIAL PATHOLOGY OF THE BLOOD. 

Table LXXIV. — Cerebral Hemorrhage {0>utiiiue4l). 











White 


Per cent 




r^• 


Affe. 


sex. 


Red cells. 


cells. 


haemo- 


Remarks. 


^ 










globin. 




43 


37 


M. 




10,300 


90 


Autopsy. 


44 


65 


M. 





10,200 


60 




45 


60 






10,200 


70 




46 


45 






9,700 


80 




47 


49 







9,300 


95 


Chronic interstitial nephritis. 
Death. 


48 


54 






8,200 


85 




49 


41 






8,100 


90 




50 


56 






7,400 


85 


Hemiplegia. 


51 


65 




953,000 


5,300 


18 


Arteriosclerosis : emphysema of 
hings : pernicious anaemia ; temp. 
102. Poly nuclear, 84.3 percent; 
lymphocytes, 13.8; eosinophiles, 
0.8; myelocytes, 0.8; basophiles, 
0.2; megaloblasts, 6. 



CAISSON DISEASE. 









White 


Per cent 




o 


Age. 


Sex. 


Red cells. 


cells 


haemo- 


Remarks. 


"^ 










globin. 




1 


29 




6,'608,00() 


52,000 
11,600 


100 


December 19th. 
December 20th. 


2 


29 






20,200 
8,900 


85 


April 15th. 

April 16th. Diff. count 500 cells? 
Polynuclear, 66 per cent; lym- 
phocytes, 33: eosinop|iiles, 0.5; 
mastVells. 0.5. 


3 








18,900 






4i 30 







10.700 






5 


42 






7,700 
19,200 
11,600 


80 


August 4th. 
August 5rh. 
August 7th. 



In a carefully studied case of intermittent claudication the fol- 
lowing counts were recorded at the Massachusetts General Hospital 



Table LXXV. — IisTermittext Claudication. 



Red cells. 



White cells. 



Per cent 
hgemoglobin. 



Remarks 



-I 

i January 18th. 
j January 20th. 
■ January 24th. 
I January 26th. 
I January 30th. 



38 



21,600 
25,200 
16,900 
10,200 
37,400 



75 



DISEASES OF THE SPINAL CORD. 387 

Table LXXV. — Intermittent Claudication {Continued). 



Age. 


Red cells. 


White 

cells. 


Per cent 
haemoglobin. 


Remarks. 






25,400 




February 4th. 






26,200 




Febniaiv lltli. 






39,100 




February 13th. 






45,700 




February 21st. 






26,200 




February 26th. 






27,400 




March 5th. 






31,600 




March 16th. 



CHOREA AND TETANY. 

Chorea showed in twelve cases normal blood except for increased " 
percentages of eosinophiles, as in Zappert's four cases, counted 630— 
1,360 (8-19 per cent) of eosinophiles. Brown ^ confirms this on the 
basis of twelve observations in a case of chorea. Eosinophiles were 
constantly increased, five to nine per cent. 

Burr ^ has made a careful study of the bjood in thirty-six cases 
and arrived at the following conclusions : There are usually a slight 
diminution in red cells and a moderate diminution in h8emoglobin. 
Any severe grade of anaemia is due to some complication. He did 
not record the leucocytes. Tetany shows no blood changes. 



DISEASES OF THE SPINAL CORD. 

Chronic diseases of the spinal cord, such as tabes dorsalis, sy- 
ringomyelia, spastic paraplegia, diffuse myelitis, paralysis agitans, 
and progressive muscular atrophy, are found to produce no changes 
in the blood, but acute myelitis may produce marked and persistent 
leucocytosis, as the following case shows : 

Table LXXVL— Myelitis. 



Age. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


30 





19,100 
16,000 
15,000 
16,000 
19,000 


90 


February 25th. Acute genera]. 
March 1st. 
March 3d. 
Marcli 5th. 
March 7th. 



^ Brown : Maryland Med. Journal, July, 1903. 
2 Burr; Univ. Med. Mag., vol. ix., p. 163. 



388 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table LXXVI.— Myelitis {Continued). 



Age. 


Red cells. 


White cells. 


Per cent 
basmoglobin. 


Remarks. 






27,000 




March 9th. 






27,900 




March 11th. 






33,500 




March 13th. 






21.600 1 


March 15th. 






21,200 


March 17th. 






24,200 


March 19th. 






22,500 ! 


March 21st. 






19.600 : 


March 23d. 






14.500 


March 25th. 






10,900 




March 27th. 

INIarch 28th. Diff. count, 500 cells: 
Polynuclear, 71.2 per cent; small 
lymphocytes. 23.6; large lympho- 
cj'tcs, 4.4; eosinophiles, 0.8; nor- 
moblasts, 1. 






13,700 


70 


March 29th. 






13,000 




March 31st. 






16,000 




April 2d: 






17.600 




April 4th. 






13.300 




April 6th. 






26,000 




April 8th. 






17,000 




April lOth. 






22,400 




April 12th. 






17,700 




April 14th. 






14,600 




April 16th. Autopsy. 



For Spinal Meningitis, see page 284. 



GENERAL PARALYSIS OF THE INSANE. 

Capps ^ has made a careful study of the blood in nineteen cases 
and conies to the following conclusions : 

1. Eed corpuscles and haemoglobin are always slightly dimin- 
ished, the averages being 4,789,900 and 85 per cent. 

2. Most cases show a slight leucocytosis — 22 per cent above the 
normal on the average. Early cases may have no leucocytosis. 

3. The polymorphonuclear leucocytes average nearly 74 per cent 
and the smaller forms of lymphocytes only 14.2 per cent, while 
the larger forms of lymphocytes are relatively numerous, averaging 
7.B per cent. In a few cases the eosinophiles were very numerous ■ 
(8.7 and 6.4 per cent). 

' American Journal of the Medical Sciences, July, 1896. 
2Roncoroni (Archiv. di Psichiat. Scien., 1894, p. 293) finds eosinophiles 
increased even to twenty-five per cent in the agitated and violent cases. 



HYSTERIA AND NEURASTHENIA. 389 

4. At the time of convulsions the red cells and hsemoglobin are 
apparently increased, due no doubt to the violent muscular con- 
tractions which raise blood pressure and concentrate the blood, or to 
cyanosis. 

There is a sudden and pronounced increase in the leucocytes 
during and after convulsions or apoplectiform attacks. That this is 
not due to concentration of the blood or to stasis Capps thinks is 
shown by the fact that not only the number, but the differential 
count of white cells shows changes, the " large mononuclear " cells 
being relatively increased, sometimes as high as 25 per cent. Mye- 
locytes were seen in one case after the convulsions, and especially 
just before death, when in a leucocytosis of 18,250 11 per cent were 
myelocytes.^ 

HYSTERIA AND NEURASTHENIA: HYPOCHONDRIASIS. 

A large number of cases have been counted at the Massachu- 
setts General Hospital with a view of excluding other diseases. 
The blood count is always normal except that in a certain numljer 
of the hysterical cases eosinophiles are relatively increased, and 
that many of the neurasthenics show the increased percentage of 
lymphocytes which I have alluded to above (page 106) as charac- 
teristic of a variety of debilitated conditions. 

Marked anceniia is seldom present, although the hsemoglobiu is 
not infrequently as low as 65 per cent. Reinert ^ found the haemo- 
globin under 60 per cent in only 4 out of 48 cases of hysteria, and 
in no7ie of 36 neurasthenics. 

The value of the blood examination in such cases, like that of 
the urine or the lungs in hysteria, is as negative evidence, and in 
this respect it is important. When the discrepancy between com- 

^ Leucocytosis has been repeatedly noticed in convulsions frojn various 
causes. Probably the irritant which causes the motor discharge also acts on 
the leucocytes by chemotaxis. For example, Barrows' study of eight cases of 
insanity with convulsions include counts of: one, 43,000 leucocytes with 92 per 
cent of polynuclears ; two, 33,000 leucocytes with 83 per cent of polynuclears ; 
three, 32,400 leucocytes with 85 per cent of polynuclears and 9 per cent of my- 
elocytes ; four, 21,500 leucocytes with 88 per cent of polynuclears. These counts 
were made immediately after a series of convulsions. The leucocj'^tosis lasted 
for many hours and showed characteristics of ordinary infectious leucocj'^tosis. 

In convulsions from improper feeding in infancy I have seen the leuco- 
cytes rise from 13,500 before the fit to 27,800 after it. 

•^Mlinch. med. Woch., 1895, No. 14. 



390 SPECIAL PATHOLOGY OF THE BLOOD. 

plaints and signs is great, we want to be doubly sure that notliiug 
hidden escapes our notice, and the blood examination is one of the 
most valuable adjuvants we have in the discovery of deep-seated in- 
flammation or malignant disease, as well as in giving us a general 
measure of the patient's degree of bodily liealth as distiuguislied 
from nervous force. The former may be higli when the latter is 
low, or both may be low, and the distinction marks out two classes 
of cases in which somewhat different treatment is appropriate. 
Tliere is no use in undertaking to make " blood and fat " when tlie 
patient has already plenty of each, tliough it may be well to carry 
out the same regime as a matter of suggestion. 



MENTAL DISEASES. 

The association of anaemia with insanity is too frequent to be a 
mere coincidence, though it i;5 hard to make either serve as a cause 
for the other. Very possibly they should both be looked upon as 
symptoms of a common underlying (unknown) cause. 

This form of anaemia has been noticed by Houston ' in melan- 
cholia and general paralysis, and by Smith" in various forms of 
insanity. 

Krypiakiewicz ^ noticed an increase of eosinophiles in acute 
forms of insanity, but not in the chronic forms. The leucocytosis 
of acute delirium " is exemplified by the following case from the 
Massachusetts General Hospital records : 

A girl of fifteen; acute delirium; leucocytes, 12,750; no food 
for eight hours; red cells, 4,510,000; haemoglobin, 63 per cent. 

Puerperal mania is to be distinguished from the delirium of 
puerperal sepsis by the fact that the latter shows leucocytosis with 
increased percentage of polymorphonuclear cells, while the former 
has no leucocytosis (if uncomplicated) and the eosinophiles are apt 
to be increased' (diminished in sepsis). 

A case of puerperal mania seen by the writer showed : Bed cells, 
5,210,000; white cells, 6,500; haemoglobin, 81 per cent; eosino- 
philes, 8 per cent. 

' Houston: Boston Med. and Surg. Journal, Januar}' 11th, 1894. 
- Smith : Jour, of Ment. Science, October, 1890. 
^Krypiakiewicz; Wien. med. Woch., 1892, No. 25. 

^Ref. in Klein -Volkmann's " Sammlung klin. Vortrage," December, 1893= 
• * Neusser: Loc. cit. 



DIABETES. 391 

As a result of 92 full and careful blood examinations in 5 cases 
of depressive-maniacal insanity, Jessie AVeston Fisher ^ comes to 
the following conclusions : 

" 1. There are no pathognomonic blood changes in cases of 
maniacal phases of manic-depressive insanity. 

" 2. Anaemia is not a causative factor nor always an accompani- 
ment of this psychosis. 

"3. The haemoglobin and red cells are frequently, if not al- 
ways, increased during an attack of excitement. 

"4. A leucocytosis is an almost constant accompaniment and, 
I believe, a result of psychomotor activity." 

At the end of three out of five cases the eosinophiles were in- 
creased. Earlier in the disease they had been low or normal. 

CONSTITUTIONAL DISEASES. 
OBESITY. 

Oertel distinguishes a plethoric and an anaemic form of obesity 
not merely clinically, but by the evidence of post-mortem examina- 
tions. He believes that there is a real overfilling of the vessels in 
the first. The second form occurs most often in women. 

Kisch examined (with v. Fleischl's instrument) the haemoglobin 
of 100 obese patients; 79 showed over 100 per cent of haemoglobin, 
1 reaching 120 per cent, while the other 21 were anaemic. 

DIABETES. 

There is nothing characteristic about the blood except the in- 
creased amount of sugar to be detected (0.57 per cent as against 
0.1 per cent normally) ; but this is not a clinically applicable test. 

Two simple tests for diabetic blood have recently attracted at- 
tention : 

1. Bremer's test: Heat thick-spread blood films to 135° C; 
cool and stain with one-per-eent aqueous solution of Congo red for 
two minutes. The blood if diabetic looks yellow to the naked eye. 
Normal blood similar^ treated looks red. Staining with methyl 
blue also shows a difference between normal blood and diabetic 
blood. The normal is blue, the diabetic yellowish-green. 

'Fisher: American Jour, of Insanity, 1903, vol. 59, No. 4. 



392 SPECIAL PATHOLOGY OF THE BLOOD. 

2. Williamson's test : Make a mixture of : 

Blood. 20 c.mni. (2 drops). 

Aqueous methyl blue (1 : 6,000) 1 c.c. 

Liquor potassse, 60 per cent (sp. gr., 1.058) 40 c.c. 

Water 40 c.c. 

Let the mixture stand three to four minutes in boiling water. 
With diabetic blood the mixture turns yellow, with normal blood it 
does not. Williamson has found this test positive in eleven dia- 
betics and negative in one hundred cases of other diseases. Bremer 
claims that by his method cases of diabetes can be recognized before 
sugar appears in the urine or after it has (temporarily) disappeared. 
Le Goff confirms the value of the test. Eichner and Folkel find 
Bremer's reaction to be as stated, but find similar color changes in 
leukaemia, Hodgkin's disease, and Graves' disease, and changes 
something like it in a variety of cachectic conditions. Badger has 
studied the blood of diabetics, leuksemics, cases of Graves' disease, 
and other cases at the jNlassachusetts General Hospital. Only in 
Graves' disease did he find reactions like those of diabetic blood. 

Table LXXVII. — Diabetes avitii Complications. 



No. 


Age. 


Red cells. 


White Per cent 
cells, jhseniosflobin. 


Remarks. 


1 

2 
3 

4 
5 
6 

7 


8 

58 
65 

22 
53 
60 





49,000 
26,000 
20,000 
14,600 
16,600 
16,300 
17,100 
17,000 
12,500 
8,200 
4,200 


52 

7.) 

.. 

75 

84 
80 
80 


Coma. 

Coma. 

April 11th. Gangreme of toes. 

April 14th. 

April 18th. 

April 22d. 

April 26th. 

Coma. 

Coma. 

Gangrene. 

Coma. 



The alkalinity has been said to be greatly diminished, especially 
in the fatal coma, but v. Noorden thinks the tests are unreliable. 

Fat is often increased in the blood up to about twelve times the 
normal, so that the serum is milky, and glycogen has been demon- 
strated niicrochemically iu the corpuscles. 



GOUT. 393 



Red Cells. 

Sugar in the blood draws water from the tissue into the vessels, 
thereby diluting the blood ; but in a short time the blood frees itself 
of the excess of sugar and fluid through increased diuresis so as to 
concentrate the blood. 

These two alternating influences serve to explain the widely dif- 
ferent counts of different observers. 

Toward the end of the disease a decided cachexia often devel- 
ops, the anaemia of which may be temporarily covered up by the 
concentration above noted, or accentuated by the dilution which 
sometimes occurs. Accordingly we may find the corpuscles increased, 
normal, or diminished in different cases or at different times with 
the same case. 

Grawitz counted 4,900,000 red cells in a patient in compara- 
tively good health, and three weeks later, when the patient had 
just been seized with the fatal coma, the count showed 6,400,000 
per cubic millimetre. With the iodine gum-arabic mixture extra- 
cellular brown stained-masses are often very much more abundant 
than in normal blood. 

The white cells show no constant changes, except that v. Lim- 
beck has noted in several cases that the digestion leucocytosis is 
unusually large even without previous fasting. Von Jaksch found 
leucocytosis in one of his eight cases, but on this point as on many 
others his results are almost unique. The only similar observation 
is that of Habershon,^ who reports moderate leucocytosis, decreased 
by strict diet. In thirteen cases I have never seen leucocytosis ex- 
cept in the presence of complications (see table, page 392). 

GOUT. 

A few cubic centimetres of serum from gouty blood made acid 
with acetic acid (six drops of a twenty-eight-per-cent solution to 
every drachm of serum) deposit crystals of uric acid on a thread in 
from eighteen to forty-eight hours; but this is not always to be 
found, and is by no means peculiar to gout.^ Uric acid is to be 
found in the blood in pneumonia, cirrhotic liver, nephritis, grave 

' St. Bartholomew's Hosp. Report, 1890, p. 153. 

^ It is important to evaporate tlie serum at a temperature not above 70° F., 
otherwise crystals will not form. 



394 



SPECIAL PATHOLOGY OF THE BLOOD. 



anaemia, leukseinia, and gravel; also in health and after a meal of 
calf's thymus or any food containing much nuclein. 

The red corpuscles show no special changes except in severe 
chronic cases, which are sometimes anaemic. The white cells are 
increased according to Neusser, while v. Limbeck and Grawitz found 
the blood wholly normal. 

It is particularly in this disease that Xeusser supposed th^^ 
"perinuclear basophilic granulations" to exist in the white cells, 
which condition he believes to be characteristic of any "uric-acid 
diathesis." Futcher has conclusively disproved this. Fibrin is in- 
creased in acute cases. 

Ewing states that he found " uniform but moderate anaemia in a 
series of chronic cases examined at Roosevelt Hospital, the patients 
all coming from the poorer classes. In the chronic cases leucocy- 
tosis of moderate grade may be observed, but it is difficult to deter- 
mine its relation to the gouty process, as many of these patients 
suffer from other complaints." I have records of only two cases, one 
a chronic case with huge tophi showed in an acute exacerbation 
21,000 leucocytes with 70 per cent haemoglobin. A severe subacute 
case showed 15,000 leucocytes. Da Costa records 14,000 in a 
single case with polycythaemia (7,125,000). 

Watson ^ records the following : 



Date. 


Leucocytes. 


Remarks. 


June 7th 


9,000 


No symptoms. 
Shght symptoms. 
At height of attack. 


June 12th 


12,500 


June 20th 


20,500 










MYXCEDEMA. 





Le Breton ^ examined the blood in one case both before and after 
thyroid treatment, and found that after forty days' treatment the 
red cells had risen from 1,750,000 to 2,450,000, the white cells 
from 4,500 to 9,600, and the hajmoglobin from 65 to 68 per 
cent. 

The remarkably high color index in this case before treatment 
(nearly 2!) corresponds with the observations of Le Breton in the 

^ Watson: Brit. Med. Jour., 1900, p. 10. 

- Le Breton: Ref, in Wien. nied. Blatter, 1895, p. 49. 



MYXCEDEMA. 



395 



dried specimen, which showed a decided increase in the size of the 
red corpuscles. He also noticed, before instituting the thyroid 
treatment, the presence of nucleated red cells and an excess of the 
polymorphonuclear form of leucocytes. Under treatment the nu- 
cleated red cells disappeared and the lymphocytes rose to their nor- 
mal per cent. 

Putnam ' has watched a similar case in which the number of red 
cells rose from 3,120,000 to 5,700,000 under thyroid treatment. 

Murray - has collected 23 cases with blood examinations. Of 
these cases, 7 showed a normal blood count, 10 were anaemic, 4 
showed leucocytosis, and 2 exhibited both anaemia and leuco- 
cytosis. 

Kraepelin ^ noticed (like Le Breton) a marked increase in the 
average diameter of the corpuscles in three cases, even when the 
count and the haemoglobin were normal. TY?dn2i {Centralbl. f. allg. 
Path., etc., April 15th, 1901) in cachexia stmrnipriva found a leu- 
cocytosis of 18,000 to 32,000 with 75 to 80 per cent of poly- 
nuclear cells, lasting for one or two weeks after the operation, 
and Mezinescu (ref. in Arch. gen. de Med., 1902, p. 743) in a 
similar case counted 49,000 leucocytes with 84 per cent of polynu- 
clear cells. 

I have had an opportunity to examine the blood in ten cases of 
this disease, but did not find anything remarkable in any one of 
them. 



No. 


Age. 


Red cells. 


AVhlte 
cells. 


Per cent 
hgemoglobln. 


Remarks. 


1 


58 

47 
41 
46 


4,700,000 

4,328,000 

4,460,000 
4,098,000 
4,062,000 

4,'670V000 
4,856,000 


11,400 
8,600 
9,800 

10,800 
8,800 
7,900 
7,900 
6,000 
6,000 
5,200 


65 

60 
80 
65 

58 

80 
87 
80 


March 21st. 


2 


April 1st. 
April 6th. 


3 




4 

5 




6 




7 




8 









Differential counts were made in five cases, and no increase in 



^Putnam: Ref. in Murray's article in "Twentieth Century Practice of 
Medicine," vol. iv. 

-Murray: "Twentieth Century Practice of Medicine," vol. iv., p. 710. 
■Kraepelin: Dent. Arch. f. klin. Med., vol. xlix., p. 587. 



396 



SPECIAL PATHOLOGY OF THE BLOOD. 



the size of the corpuscles, such as Le Tireton and Kraepelin saw, 
was present in these cases. The count showed : 



Case. 


Polymorphonuclear 
cells. 


Lymphocytes. 


Eosinophiles. 


1 


67.0 
67.0 
74.0 
66.0 

77.3 


28.0 r,.o 


2 


27.8 
26.0 
81.5 
21.6 


4.4 


3 




4 


2.5 





.6 







The increase of eosinophils in two of these cases may 2:>eiha})S 
be due to the skin troubles in the disease. 

J. J. Thomas found a few myelocytes in a case of Putnam's. 

CRETINISM. 

Koplik ^ records the following in two cases of sporadic cretinism : 
Case I. — Fifteen months old; advanced stage of disease. Hae- 
moglobin, 18 per cent. 

Case II.— Eed cells, 3,026,000; white cells, 1.3,500; haemoglo- 
bin, 105 per cent. This high haemoglobin corresponds to nornwl 
fmtal blood. The child was nine weeks old. but its backward de- 
velopment is mirrored in the blood. As tlie case improved under 
thyroids the haemoglobin came down. 

GRAVES' DISEASE (BASEDOW'S DISEASE; EXOPHTHALMIC 

GOITRE). 

The blood is normal, except for an occasional associated chlorosis 
and sometimes a marked lymphocytosis. In one case I found 51.3 
per cent of lymphocytes and 1 per cent of myelocytes in 1,000 leu- 
cocytes, the polymorphonuclear cells being only 48 per cent; Imt in 
fourteen other cases I have never found this again. The same fact 
has been noticed by Neusser (cited in Klein, loc. cit.). 

Oppenheimer '^ found the red cells and haemoglobin normal in 
two cases. Yon Jaksch ^ in one case •• complicated with myxoe- 
dema" found 3,818,000 red and 8,000 white ceHs. 

The association of Graves' disea^^e Avitji chlorosis is illustrated 
by two cases from Zappert : ^ 

1 New York Medical Record, October 2d, 1897. 
^Deut. med. Woch., 1889, p. 861. 
^Zeit. f. klin. Med., 1893, p. 187. 
^Zeit. f. klin. Med., 1893, p. 266. 



. 



GRAVES' DISEASE. 



397 



Case. 


Red cells. 


White cells. 


Per cent 
Haemoglobin. 


1 


2,858,000 
2,738,000 


3,800 
3,800 


32 


2 


30 







The same writer found eosinophiles increased (8.5 per cent) in 
one out of four cases. 



Table LXXVIII.— Massachusetts General Hospital Cases. 



Age, 

44 
36 

42 
39 
27 
42 
34 
31 
51 
33 
19 



12 46 

13 28 
14' 41 
15 44 



16 



35 



Sex. 
M. 



Red cells. 



3,668,000 



4,920,000 



4,464,000 



4,584,000 



3,433,000 



White 
cells. 


Per cent 
hasmo- 
globin. 


2,800 


45 


5,600 


80 


6,800 




7,000 


75 


7,100 


70 


7,300 


65 


7,700 


60 


8,500 


85 


8,700 


80 


9,800 


90 


9,800 


63 


10,200 


80 


10,500 


80 


11,500 


70 


11,600 


90 


12,500 


50 


12,700 




16,000 


56 


15,000 




14,400 


70 


7,600 




6,800 




17,800 


50 


23,100 


70 


21,400 


•• 



Remarks. 



March 29th. 
May 20th. 



Died. 



January 13th. 
January 31st. 
February 13th. 
February 15th. 
March 1st. 
March 8th. 
March 15th. 

February 10th. 
February 11th. 



Table LXXIX. — Goitre Without Exophthalmos. 



No. 


1 
Age 


1 


46 




21 


3 


17 


4 


51 


5 


45 



Red cells. 



White 
cells. 



Per cent 
hgemoglobin 



Remarks. 



5,448,000 



12,000 

11,000 

7,400 

6,600 

5,800 



75 
80 
55 
90 



398 SPECIAL PATHOLOGY OF THE BLOOD. 

ADDISON'S DISEASE. 

Some, but not all, cases are accompanied by marked anaemia. 
Neumann ^ observed a case in which the symptoms came on acutely 
and the red cells sank to 1.120,000 per cubic millimetre. During 
the convalescence which followed, the cells ran up above normal, 
reaching 7,700,000. 

Tschirkoff ^ reports two cases in which the red cells were re- 
spectively 3,280,000 and 2,933,000 at the lowest, but whose haemo- 
globin was extraordinarily high, over 100 per cent in one case. 
This he found on spectroscopic examination to be due to a great in- 
crease of reduced haemoglobin in the corpuscles. Methaemoglobin 
was also noted. 

The white corpuscles showed no changes, quantitative or quali- 
tative, except that they contained l)lack pigment granules. Three 
cases have been examined at the jNIassachusetts General Hospital. 
The first, a woman of thirty, showed 6,240,000 red cells with 14,- 
000 white, and 90 per cent of haemoglobin. The differential count 
of 90 leucocytes showed the following figures : Polymorphonuclear 
cells, 53.4 per cent; lymphocytes, 41 per cent; eosinophiles, 4.."> 
per cent; myelocytes, 0.9 per cent. 

The eosinophiles w^ere very large, some of them eosinophilic 
myelocytes. 

The second, a man of forty-two, was very anaemic and weak at 
entrance and showed: Eed cells, 2,196,000; white cells, 7,500; 
haemoglobin, 20 per cent. Differential count of 200 leucocytes 
showed: Polymorphonuclear cells, 65 per cent; hmiphocytes, 31.5 
per cent; eosinophiles, 3.5 per cent; 5 normoblasts; marked poiki- 
locytosis. 

Under suprarenal extract his blood improved in a month till his 
red cells numbered 4,700,000; white cells, 9,000; haemoglobin, 6o 
per cent. 

The third, a man of fifty-two, showed : October 20th — red cells, 
2,848,000; white cells, 4,800; haemoglobin, 45 per cent. Decem- 
ber 10th— red cells, 2,624,000; white cells, 7,100; haemoglobin, 
45 per cent. Differential count : Polynuclear, 74 per cent; small 
lymphocytes, 22 per cent; large lymphocytes, 4 per cent; eosino- 
philes, 0.4 per cent. No nucleated red cells. 

iNemiiann: Deut. mecl. Wocli., 1894, p. 105. 
-Zeit. f. klin. Med., 1891, vol. xix., Suppl.-Heft 37. 



DISEASES OF BONE. 



P>99 



A fourth patient, kiudly sent me by Dr. Kogers, of Dorchester, 
showed: Red cells, 2,864,000; white cells, 2,000; haemoglobin, 51 
per cent. Differential count of 300 cells showed : Polymorphonu- 
clear cells, 63.3 per cent; lymphocytes, 33.3 per cent; eosinophiles, 
2.3 per cent; basophiles, 0.3 per cent. 

Brown ^ mentions 2 cases wdth 4.4 per cent and 8 per cent of 
eosinophiles (286 and 960 absolutely). 

I have never seen melanin in the leucocytes as Tschirokff did in 
his two cases. 



Table LXXX. — Addison's Disease (Additional Cases). 



Age. 


Red cells. 


White cells. 


Per cent 
haemoglobin. 


Remarks. 


34 
39 
29 


5,056,000 
5,460,000 
4,804.000 

519,200 


5,000 

7,000 

10,000 

10,400 


60 

80 • 
68 

80 


Soon died. 
Autopsy. 

Polynuclear, 77.6^. 
Lymphocytes, 14.0 
Eosinophiles, 8.0 
Myelocytes, .4 



DISEASES OF BONE. 
Table LXXXI. — Osteo- Arthritis. 



No. 


Age. 


1 


58 


2 


63 


3 


53 


4 


29 


5 


52 


6 


52 


7 


21 


8 


52 


9 


47 


10 


53 


11 


48 


12 


36 


13 


35 



Red cells. 



3,552,000 



4,968,000 



White 
cells. 



49,000 

32,000 

35,000 

28,800 

24,000 

22,500 

18,000 

23,000 

20,400 

14,600 

12,000 

11,200 

11,000 

10,800 

10,000 

9,800 

9,000 

9,000 

8,700 



Per cent 
hasmoglobin. 



50 



80 
70 
70 
85 
70 
85 
100 
85 
85 
65 
85 
80 



Remarks. 



November 11th. 

November 12th. 

November 14th. 

November 17th. 

November 20th. 

November 23d. 

December 8th. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 

Spine. 



Spine. 



' Internat. Clinic, vol. iv., 12tli series. 



400 SPECIAL PATHOLOGY OF THE BLOOD. 

Table LXXXI. — Osteo-Arthritis {^Continued). 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemoglobin. 


Remarks. 


14 

15 


37 

42 




6,600 
5,200 


90 

75 


Spine. Diff. count: Polynuclear, 
62 per cent ; small lymphocytes, 
30; large lymphocytes, 7 ; cosino- 
philes, 1. 

Spine. 



Table LXXXII.— Osteitis Deformans. 



No. 


Age. 


Red cells. 


White 
cells. 


Per cent 
haemoglobin. 


Remarks. 


1 


45 




7,000 


80 


February 6th. 






4,480,000 


10,000 


75 


February 8th. 


2 


49 


5,330,000 


7,200 


65 


Diff. count: Polynuclear, 66 per 
cent; small lymphocytes, 33.5; 
large lymphocytes, 33.5; eosino- 
philes, 5. 


8 


37 




8,600 


90 





FRACTURES. 

Thirty-five cases of fractures studied by Cabot, Hubbard, and 
Blake (loc. cit.) showed nothing abnormal. 

OSTEOMALACIA. 

The blood has a long time been supposed, on the authority of v. 
Jaksch (Zeit. f. klin. Med., vol. xiii., p. 360), to exhibit a dimin- 
ished alkalinity, the bones being supposed to be eaten away by 
acids in the blood. Yon Limbeck and many other observers have 
lately shown that the blood is normal in alkalescence. 

Corpuscles and haemoglobin are usually within normal limits 
quantitatively, but Neusser reports an increase of eosinophiles und 
the presence of myelocytes in the blood. 

Eitchie * confirms Neusser and found also that the lymphocytes 
were more numerous than normal. 

Fehling,^ Sternberg,^ Chrobak'^ found no increase of eosin- 
opliiles. 

Rieder's case was normal in all respects: Eed cells, 4,892,000; 
white cells, 5,600; eosinophiles, 3.6 per cent; polymorphonuclear 
cells, 61 per cent. 

^ Edin. Med. Journal, June, 1896. 
2 Cited by Ritchie: Loc. cit. 



RICKETS. 401 

Ewing says : " The usual condition of the blood in osteomalacia 
appears to be that of moderate secondary anaemia. The leucocytes 
have varied from subnormal to moderately increased numbers. The 
lymphocytes are usually very numerous, an excessive proportion 
(maximum 56 per cent) having been found by Tschistawitch. High 
normal proportions of eosins have been found by several observers, 
but not by others." 

RICKETS. 

1. Anaemia is always present in severe cases and often in moder- 
ate ones. This, together with the fact that many cases of rickets 
are associated with an enlargement of the spleen, has led to the use 
of the misleading term "splenic anaemia." There is no form of 
anaemia found in rickets that may not be found in other conditions 
(Morse) . ^ 

Hock and Schlesinger found an average of 2,500,000 red cells 
in a considerable number of cases with and without enlarged spleen. 

Ton Jaksch describes a case in which the red cells sank from 
1,600,000 to 750,000 within three months, and Luzet saw a simi- 
larly rapid process, the cells falling from 2,110,000 to 1,596,000 
within three weeks. On the other hand, in Morse's admirable 
study of twenty well-marked cases the red cells averaged over 
4,500,000 and not a case fell below 3,500,000. 

2. The haemoglobin is always relatively low; it averaged 63 
per cent in Morse's cases, a color index of about 0.7. Felsenthal 
got similar results. 

White Corjjuscles. 

It is often difficult to say whether or not the leucocytes are in- 
creased, owing to the occurrence of most cases in infants at an age 
when leucocytes are always higher than in adults — how much higher 
at any given age depends largely upon the degree of vigor and for- 
wardness of development of the individual child. 

In Morse's series, for example, the average age of the infants is 
twelve months. And for this age none of the counts in his series 
seems to me necessarily abnormal. They are all under 16,000 ex- 
cept three, these three being 17,900, 18,800, and 22,000 respectively, 
the latter in a nine months' infant. Many of the counts seem to 
me subnormal for infancy (5,500, 7,200). Most observers find leu- 
cocytosis present in many cases, but not in all. 

» Morse. Boston City llosp. Rep,, 1897. 
26 



402 SPECIAL PATHOLOGY OF THE BLOOD. 

Qualitative Changes. 
Red Cells. 

As in all ansemias of infants, the '' degenerative " and -'regener- 
ative" changes are relatively common. 

Polychromatophilic forms and nucleated corpuscles are fre- 
quently to be found, the latter often in great numbers but with a 
majority of the normoblast type. 

White Cells. 

Lymphocytosis is said to be marked, but, as with the question 
of leucocytosis, we are never quite sure whether the numbers are 
abnormal /or that age^ for lymphocytosis is the normal condition in 
infants' blood. 

When, however, as in a case mentioned by Rieder, we find 75 
lymphocytes in every 100 leucocytes, the child being four years old, 
we are surely dealing with a pathological condition. Another of 
his cases, a seven-months' child, rachitic, with 57 per cent of lym- 
phocytes, seems to fall within normal limits. Not so with Morse's 
cases. The highest percentage of lymphocytes in his series was 69, 
in an infant of two months. I have similar counts in health at that 
age. The average of his twenty cases is 43 per cent, which is, if 
anything, rather low for that age. The same difficulty arises with 
regard to the reports of eosino2)hil'm in rickets, since eosinophiles 
are always relatively numerous in infancj^ Morse's highest figure 
was 7 per cent, his average 3 per cent. Hock and Schlesinger found 
20 per cent in one subject, and Weiss 16 per cent in another. 
They were highest in cases with splenic tumor. In Eieder's four 
cases and in the three seen at the Massachusetts General Hospital, 
no eosinophilia was present. Myelocytes in small numbers (0.5-0,2 
per cent) are not uncommon, and may be considerably more nu- 
merous. 



CHAPTEE IX. 

HEMORRHAGIC DISEASES. HAEMOLYSIS AND BLOOD 

POISONS. 

PURPURA HEMORRHAGICA. 

The blood is practically that of aneemia from hemorrhage (red 
cells and haemoglobin reduced, white cells increased, occasional nu- 
cleated red corpuscles or polychromatophilic forms). Agello ^ has 
found methaemoglobin in the blood, and hence concludes that the 
disease is a poisoning of the corpuscles by ptomains absorbed from 
the intestine. 

The blood plates are much diminished and may be entirely ab- 
sent in the worst stages. 

Bacteria of various kinds have been reported in the disease, but 
negative results are also common, and their presence is probably 
not significant. 

The red cells may fall as low as 2,500,000, but are much oftener 
slightly or not at all diminished. In many mild cases there are no 
demonstrable blood changes. On the other hand, Osier mentions a 
case which sank to 1,800,000, and in Muir's case the count reached 
800,000 with 11 per cent of haemoglobin. The loss of blood may 
give rise to a fatal anaemia of the microcyte type (see page 146). 
In a GSiSe of acute infectious purpura ("typhus angeiohematique ") 
Barjon and Cade (Soc. d. Biol., 1901, p. 246) found 85,000 leuco- 
cytes (94 per cent polynuclears) at the outset, gradually falling to 
normal within two weeks. The red cells fell to 2,027,000. 

Bensaude ^ has observed that in 16 cases characterized by large 
hemorrhages (2 = acute "infectious," 2 with tuberculosis, 2 chronic, 
10 = Werlhof's disease) the clot shows no retraction and no transu- 
dation of the serum. Cases with small hemorrhages (toxic, rheu- 
matic, cachectic, and nervous) do not show any such abnormal char- 
acteristics. Hence he concludes that at the outset of a case of 

iRiforma Med., Napoli, 1894, p. 103. 
2 La Semaine Med., 1897. p. 21. 



404 SPECIAL PATHOLOGY OF THE BLOOD. 

purpura, observation of the clotting process nui}' enable us to fore- 
tell whether or not the case is to be of a severe or of a mild t3'pe. 
He found the V)lood lesion above described to be greatest during the 
hemorrhagic crises, slowly disappearing between them. Hayem 
has confirmed these observations. He finds the fibrin network 
almost invisible. Despite this and despite tlie absence of contrac- 
tion in the clot, the actual rate of clotting is normal. Hayem lias 
seen similar failure of contraction when the blood plates are plenty. 
It occasionally occurs in symptomatic purpura {<'.'j., from phthisis). 

SCURVY. 

There are no characteristic blood changes known. When liemor- 
rhage is severe the red cells may sink very low,— to 370,000 as in 
T alley 's ^ case, to 557,875 in a case of Houchut's; ' Ouskow ^ and 
Hayem saw counts of 3,500,000 and 4,700,000. Talley has re- 
cently collected from the literature several cases witli less than 
2,000,000 red cells per cubic millimetre, but the average of the counts 
of seven observers (see Talley's bibliography) was between 3,000,000 
and 4,000,000. The usual qualitative changes of secondary anaemia 
are present in severe cases; the haemoglobin suffers as usual more 
than the count of red cells and is slow in regeneration. 

Leucocytes may be increased, whether from hemorrhage or from 
some complicating inflammatory process, but in uncomplicated 
cases they are usually reduced {e. g., 4,700 in Talley "s case). 

" The red cells vary in number and size according to the length 
and severity of tlie disease. On account of the frequenc}^ of inflam- 
matory complications and hemorrhages tlie leucocytes are usually 
increased, Ouskow ^ finding them as high as 47,000, Henry ' 20,000 
in two cases, and Stengel ^ 40,000 (after hemorrhages) with lympho- 
cytosis. Litten, however, observed no leucocj^tosis, and the writer 
in two well-marked but uncomplicated cases found no increase " 
(Ewing). In a single case I recorded: lied cells 3,600,000; white 
cells, 3,600, haemoglobin 40 per cent, 

^Tallej: Jour. Am. Med. Assn., Xovember 1st, 1902. 
^Boiichut: Gaz. des Hop., 1878, p. 1187. 
2 0-^skow : Centralbl. f . inn. Med. 1878. No. 28. 
■i Henry: Phil. Hosp. Rep., 1890, p. 125, 
^Steno^el; "Twentieth Cent. Pract.," vol. vii. 



HEMOLYSIS AND BLOOD POISONS. 



405 



INFANTILE SCURVY (BARLOW'S DISEASE). 

Da Costa in 7 cases found the haemoglobin ranging from 35 to 
65 per cent (average 43 per cent), and the red cells from 2,950,000 
to 5,100,000 (average 3,527,000). Only one case showed leucocy- 
tosis, the average in 7 being 15,500. The lymphocytes in 4 of 
the 7 were between 60 and 65 per cent. The eosinophiles were 
normal or low, and myelocytes 1 to 6 percent (average 2.5 per cent). 

Barlow's disease may lower the red cells as far as 976,000— as 
in a case of Reinert's — the haemoglobin being 17 per cent and the 
white cells 12,000. This was the day before death. The blood 
plates are not diminished, and the clot retracts normally 



HAEMOPHILIA. 

The blood changes are practically those just described and show 
nothing characteristic of the disease. Coagulation is slower than 
normal and blood plates are sometimes very scanty. The white 
cells are sometimes persistently diminished, as in the following 
cases : 

I. 





Sept. nth. 


Sept. 14th. 


Sept. 17th. 


Sept. 30th. 


Sept. 23d. 


Sept. 34th. 


Red cells 

White cells 


3,960,000 
3,400 

43 per cent. 


3,400 


3[m 


3,'900 


3,700 
64 per cent. 


3,800,000 
3,300 


Hasmoglobin 


49 per cent. 




II. 




February 8tli. 


February 38th. 




4,400,000 
5,000 

30 per cent. 


3,600,000 
5,000 

28 per cent. 


!► Daay nose-bleed. 



HEMOLYSIS AND BLOOD POISONS. 

The subject is a very extensive one, and I shall not attempt to 
review the magnificent work of Ehrlich and his pupils except where 
it concerns the field of practical blood diagnosis. For clinical pur- 
poses blood poisons are conveniently divided into three classes : 

I. Those that produce haemolysis alone. 

II. Those that produce methaemoglobinaemia and haemolysis. 



408 SPECIAL PATHOLOGY OF THE BLOOD. 

TIL Those that poison the blood by forming a chemical union 
Avith the red cells (other than methsemoglobin) and so interfere 
with their functions. 

I. HEMOLYTIC Agents. 

Among the agencies which produce lismolysis the most impor- 
tant are : 

1. Infectious diseases, especially malaria and yellow fever; less 
often severe sepsis, typhoid, scarlet fever, and Weil's disease. 

2. In the course of exhausting diseases such as nephritis, cir- 
rhosis, and those leading to chronic icterus, autohsemolytic sul)- 
stances are not infrequently formed in the system; so also in puer- 
peral eclampsia (Hayem) in the new-born (Winckel's disease), and 
after the absorption of peritoneal hemorrhage from extra-uterine 
pregnancy. 

0. Poisons of vegetable origin — such as those contained in many 
species of mushrooms, aspidium, felix mas, saponin substances, 
i.e., tlie giucocides contained in Quillaja saponaria, the Alpine 
violet (Cyclamen Europseum), various species of solanvim {night 
shade, etc.), various arrow poisons. Probably akin to these are: 

4. Snake jyoisons and scorpion poison and 

5. Guiacol, and quinine under certain conditions. 

6. Haemolysis results from the transfusion of alien blood or of 
saline solutions not isotonic, from inhaling AsHg and rarely from 
severe burns. 

7. Under conditions very little understood influences such as 
cold, fatigue, or emotional strain produce in certain individuals sud- 
den brief haemolysis to the results of which we give the name of 
■paroxymal hcemogloblnmnila. 

The process of haemolysis includes : 

1. Separation of the haemoglobin from the corpuscles so that it 
colors the serum. 

2. Actual breaking to pieces of the red cells without separation 
of the haemoglobin. 

If normal blood is drawn and left to stand, the serum whicli 
separates from the corpuscles is not red-tinged or but very slightly 
so, provided all shaking and jarring are avoided. A very slight 
reddish tinge may appear in the serum even with most careful tech- 
nique. In some conditions the haemoglobin, while not actually 
separated from the corpuscles within the vessels, is so loosely con- 



HEMOLYSIS AND BLOOD POISON. 



407 



nee ted to them that a considerable quantity separates post mortem 
and colors the serum in spite of the avoidance of any jar. 

This condition is to be distinguished from true haemoglobinaemia, 
in which the serum is actually colored before leaving the vessels, 
although the two conditions really represent only different degrees 
of vulnerability of the red cells. 

We are surer of a diagnosis of haemogiobinsemia when we find 
bits of broken-down cells in the fresh blood and the additional evi- 
dence of hsemoglobinuria or jaundice. 

The Blood in Paroxyiiial Hcemoglobinwinia. 

Coagulation is very rapid, but the clot soon dissolves again 
(Hayem). The fresh blood occasionally shows deformities in the 
corpuscles or bits of broken cells, and lack of rouleaux if examined 
(luring a paroxysm. As a rule the corpuscles of the peripheral 
blood look normal. Frazer has recently reported a case in which 
lie excited a paroxysm by a cold bath, and studied the blood with 
<rreat care. 



Time. 


Red cells. 


White cells. 


Per cent 
hasmoglobln. 


Blood plates. 


10 A.M. Before bath 

11 :05 A.M. Twenty - five 

minutes after bath; 

urine pale. 

11:45 (urine dark) 

1:15 P.M 


4,075,000 

3,633,300 
3,760,000 
4,200,000 
3,800,000 
4,100,000 


15,000 

21,800 
21,300 
21,500 
17,700 

18,700 


50 

50 
60 
50 
50 
50 


450,000 

696,000 
525,000 
4,250.000(1) 
1,600,000 


3:45 P.M 


l^ext day, 1 p.m 


500,000 







The enormous increase of "blood plates" is striking. It is 
difficult to resist the conclusion that these blood plates were bits of 
broken red corpuscles. The serum was current- jelly colored. The 
appearance of the corpuscles was quite normal. 

The Blood iii Severe Burns. 

I have no personal experience with cases in which haemolysis 
has been demonstrated. Locke's ^ careful study of ten cases and 
of the literature led him to the following conclusions : 

1. The blood flows sluggishly and is of a peculiar dark purple 
appearance. 

J Locke: Boston Med. and Suro-. Jour., October 30th, 1903. 



408 SPECIAL PATHOLOGY OF THE BLOOD. 

2. All immediate increase in the number of erythrocytes, in 
severe but not fatal cases, of from 1,000,000 to 2,000,000 per 
cubic millimetre takes place within a few hours; in fatal cases 
there is an increase of from 2,500,000 to 4,000,000 per cubic 
millimetre. 

3. A rapidly increasing leucocytosis occurs in all cases; in those 
ending in recovery the increase is often 30,000 or 40,000 per cubic 
millimetre; in fatal cases usually above oO.OOO per cubic milli- 
metre. 

4. Morphological changes in the erythrocytes are slight. 

0. The percentage of neutrophiles is somewhat above the nor- 
mal, but not so much as in the ordinary inflammatory leucocytosis. 

6. A considerable destruction of the leucocytes takes place, espe- 
cially in the very severe burns. 

7. Myelocytes may be present in small" numbers in severe 
cases. 

8. There is, as a rule, marked increase in the number of blood 
plates. 

The table on page 409 shows Locke's results in detail. 

Ether Inhahiflon. 

Da Costa and Fish (loc. cit.) have shown that in anaemic pa- 
tients ether narcosis may produce a considerable diminution in the 
red cells and haemoglobin presumably through haemolysis (see 
above, page 253). 

II. Poisoxs Producixg Meth.emoglobix.emia avith axd with- 
out HEMOLYSIS. 

One of the most important is : 

1. Chlorate of Potash. — This destroys the corpuscles and pro- 
duces haemoglobinaemia and the usual train of symptoms (jaundice, 
dark urine, etc.) due to this. 

Brandenburg ' examined the blood of a woman who had taken 
two and one-half ounces of chlorate of potash in water the night 
before. The blood showed marked leucocytosis and broken and dis- 
torted red cells. In gross it was chocolate-colored and the serum 

^ Berliner kiln. Woch., 1895, Xo. 27. 



hji:molysis and blood poisons. 



409 



•juao 






:^::?5 ;:s :^ :s ^:5; 



•■\Ud'J 

jad 'saiiqdouTSoa 






•^ueo J8d 

'IBUOIJISU'BJl, 






■^uao jad 'aga^i 



-*$:- i- N r-1 -^ d rl ?1 iH M l-H i:0 N (M CO t-^ t- t-H 






•^nao 
jad 'saniidoa^naM 






•sapsnd 
-joo aatqA\ !junoo 



ggggooggggoooogogooc 



•sapsnd 
-JOO pooiq paj junoo 



SOgogo=oosg< 



• O 






sss 



•}xtao 
aad 'mqoiaomaBH 



L^ CO • Q • . ■ CO • • - 

C;C^-0---01--- 



S^S 



II 



!3 

a 

a 



oo'3ooooooooot:oooo 



OJ 02' 



3 3 3 3 3 i=l 



•—11—1 5^it-05 tHCOi— IM 



22 
3 3 
o o 



r-l OJ CO 



000 

;2; z ^2; 



■^lO «0 i- OCOirH 



410 SPECIAL PATHOLOGY OF THE BLOOD. 

after separation of the clot was brown. The red cells progressively 
decreased as follows: 

Red cells. ^Vhite cells. 

First day 4,300,000 20,000 

Second day 2,500,000 

Fourth day 2,300,000 

Fifth day 2,100,000 

Sixth day 1,900,000 

Seventh day 1,600,000 15,000 (death). 

Jacob ' studied a similar case : Thirty hours after a dose of 25 
gm. of KCIO3 the blood showed : Eed cells, 4,425,000; white cells, 
80,000 (stained specimen resembles leukaemia). Next day, red 
cells, 1,825,000 (broken and decolorized;; white cells, 60,800 
Fourth day, red cells, 2,225,000; white cells, 14,000. 

2. Ehrlich and Lindenthal " report the case of a patient who was 
poisoned with nitrobenzol. Ten hours after the blood was choco- 
late-colored and showed methsemoglobin bands. Under the micro- 
scope there were no changes till the third day, when poikilocytosis 
appeared. 







Per cent 


Nucleated 


Red cells. 


White cells. 


haemo- 


red cells 






globin. 


per cubic 
millimetre. 


2,275,000 


Much increased. 


55 


2,070 


1,845,000 


ii a 


50 


7,900 


1,600,000 


" " 


44 


24,700 (!) 


905,000 


u u 


40 


12,000 


1.102,000 


u u 




1,300 


900,200 


a u 


•• 


540 



Fifth day 

Seventh da}^ 

Eleventh daj^ 

Fifteenth day 

Seventeenth day 

Nineteenth day 

Nineteenth day, death. 



The nucleated red cells were at first mostly normoblasts; later 
mostly megaloblasts. Posselt^ and Boas "* have published similar 
cases. 

3. Antipyrln and Acetanilid, — A patient of P. K. Brown,' five 



1 Berl. klin. Woch., 1897, No. 27. 

2 Zeit. f. klin. Med., 1896, p. 427. 
3Wien. klin. Woch., 1897, No. 30. 
^ Deut. med. Woch., 1897, No.. 51. 

^ Brown : Am. Jour, of the Med. Sciences, December, 



1901. 



HAEMOLYSIS AND BLOOD POISONS. 



411 



days after taking sixty grains of acetanilid showed the following 
blood : 



Haemoglobin. 1 


Erythrocytes. 


Leucocytes. 


Nucleated 
red cells. 


5th dav of illness, 40 per cent 

6th " '' " 35 " 

7th " '' 33 " 

8tli " " 32 " (death) 


2,200,000 
1,490,000 
1,400,000 
1,166.000 


62,400 
62,935 
51,400 
66,450 


17,600 
25,705 
19,000 
22,150 



Table LXXXIII. — Differential Counts. 





NrCLEATED RED CELLS. 




(Seen during a count of 500 ' 




leucocytes.) 




Megalo- 


Normo- 


Micro- 




blasts. 


blasts. 


blasts- 1 

1 


5th dav 


39 


60 


1 


6th day 


15 


73 


12 


7th day 






, 


8th day 


19 


65 


16 1 


(death) 






1 



Leucocytes 



Polymorpbo-. Large 
nuclear. lymphocytes 



70 per ct. | 26 per ct. 
59 " 



57 



30 
35.6 



Small 
lymphocytes. 



4 per ct. 
9 " 

6.5 " 



Eoslno- 
philes. 



Among the largv l3'niphocytes are inclnded a considerable per- 
centage of myelocytes. 

The si)ecimen of the fifth day showed the direct action of the 
poison on the red cells. The cells were of all sizes and shapes, the 
microcytes showing an nnusual sort of distortion, unlike crenation 
or the changes in microcytes of pernicious anaemia, and the megalo- 
cytes haying no distortion and resembling strikingly those of per- 
nicious anaemia. Indeed, as the process advanced the picture of the 
red cells grew more and more like pernicious anaemia. The average 
diameter of the cells increased, the microcytes grew fewer in num- 
ber and showed less distortion, and the color index rose very 
high.'- 

In Stengel's ^ chronic case of acetanilid poisoning, which eventu- 
ally recovered, the red cells fell to 2,092,300 with 35 per cent of 
hemoglobin and 39,100 leucocytes. Of the red cells 32,000 per 
cubic millimetre were nucleated, nine-tenths of them beins: iiormo- 



^ By yon Kahldeu's method. 

- Compare similar results obtained experimentally by Roseuqyist (" Blut- 
giftauamieu," Helsingfors, 1900. 

3 Stengel: Uniy. Penn. Med. Bull., February, 1903. 



412 SPECIAL PATHOLOGY OF THE BLOOD. 

blasts. Every known anomaly of staining reaction was present. 
T. E;. Brown ' mentions an acute case with 12 per cent of eosino- 
philes (3,600 absolute). 

There may be no definite evidence of haemolysis or anaemia, and 
the only symptoms may be cyanosis and general weakness. In a 
chronic case which I have recently reported ■' the red cells varied 
between 5,000,000 and 6,090,000 with from 16,000 to 29,800 leuco- 
cytes. Methsemoglobin bands were present on spectroscopic exami- 
nation and the blood in gross was cliocolate-brown. The differential 
count showed a simple polynuclear leucocytosis (83 to 92 per cent); 
the eosinophiles were always diminished, sometimes absent. The 
red cells showed a good deal of basophilic stippling and very slight 
poikilocytosis, but no other peculiarities. There was no demon- 
strable haemolysis. 

4. Phenacetin poison iiKj (l^vomg: BerJ. klin. irocA., 1895) may 
cause actual blood destruction with anaemia in case the patient sur- 
vives the immediate effects of the deprivation of oxygen. Similar 
accidents have occurred with phenocol and lactophenin (3 gm, per 
day — Grawitz). 

5. Workers in aniline dyes and nitroglycerin factories may V)e 
severely poisoned by nitrohenzol compounds inhaled and producing 
methsemoglobinaemia. 

6. Fyrogallic acid and 'pyrogallol as used in treatment of skin 
diseases may lead to death through destruction of the red cells. 
Chromic acid (for instance, as applied through the vagina) may have 
a similar effect. 

Many other less common substances work the same ill effects on 
the blood. 



III. Substances Injuring the Function of the Bed Cells 
WITHOUT Producing Hemolysis or Methemoglobinemia. 

The substances in this group, of which carbonic oxide gas 
is the type, poison by combining chemically with the haemo- 
globin and preventing its combination with the oxygen of the 
air. 

Illuminating gas is for our purposes the most important. 

^ T. R. Brown: Internat. Chnics, vol. iv., 12th series. 
2 Cabot: Phil. Med. Jour., November 39th, 1902. 



H^.MOLYSIS AND BLOOD POISON. 413 

The appearance of individual blood cells is not altered nor do 
they break up, but the corpuscles are useless to breathe with, as 
they cannot take up oxygen. 

The color of the blood is very bright red, much brighter than 
normal. Spectroscopic examination shows absorption bands of car- 
bonyl-hsemoglobin which are characteristic if not reduced by am- 
monium sulphide. Their position in the spectrum is very close to 
that of the oxyhsemoglobin bands and without the chemical test 
mistakes may occur (Yarrow)/ 

Red Cells. 

Von Limbeck' found in two cases 6,630,000 and 5,700,000 re- 
spectively. The volume of these corpuscles (estimated by Bleib- 
treu's method) was greatly increased, amounting to 70.7 per cent 
(normal, 41-48 per cent), so that apparently the size of the indi- 
vidual cells is increased. 

Miinzer and Palma^ found 5,700,000 red cells in one case. 

In a chronic case reported by Yarrow (loc. cit.) there was anae- 
mia (3,700,000 red cells) with a moderate leucocytosis and 8 per 
cent of myelocytes. The other leucocytes were present in normal 
percentages. 

Ehrlich found numerous normoblasts in one case, though no 
anaemia was present. The presence of normoblasts and myelocytes 
under these conditions points to a stimulation of the bone marrow, 
possibly to make up for some haemolysis of which we have no direct 
evidence. 

Leucocytes. 

Eaton * reported four cases, in all of which the white cells 
were increased, the counts ranging between 15,000 and 22,000 
per cubic millimetre. Da Costa's case had 32,000 leucocytes 
with 92 per cent polynuclears and 1.5 per cent myelocytes (480 
absolute). 

Miinzer and Palma (loc. cit.) found 13,300 in their case. 

VYarrow: American Med., August SOth, 1903. 

'^Loc. cit., p. 234. 

sZeit. f. Heilk., vol. XV., p. 1. 

4 Boston Medical and Surgical Journal, March I4th, 1895. 



414 



SPECIAL PATHOLOGY OF THE BLOOD, 



Twenty-eight such cases have been examined at the Massachusetts 
General Hospital with the following results : 



Table LXXXIV.— Illuminating Gas Poisoneng. 



c3 


Age. S( 


;x. 


^ 






1 


41 J 


^I. 


3 


49 J 


^. 


3 


21 1 


H. 


4 


45 




5 


19 J 


\i. 


6 


50 




7 


40 I 


^. 


8 


Adult 




9 


60 : 


vi. 


10 


25 I 


^. 


11 


45 I 


^. 


12 


Adult 




13 


64 




14 


24 




15 


16 ] 


T' 


16 


27 




17 


50 




18 


22 


. 


19 


19 I 


VI. 


20 


56 




21 


21 




22 


19 




23 


55 




24 


28 




25 


33 


. 


26 


19 




27 


20 




28 


25 





Red cells. 



4,930,000 



White 


Per cent 


cells. 


haemo- 




globin. 


31,200 




27,100 




19,900 




26,000 


70 


25,600 


100 


25,470 


97 


25,200 




22,900 


75 


21,200 




15,500 




22.000 




20,400 


75 


20,360 


100 


20,100 


_ 


20,000 




19,600 


80 


18,800 




18,500 


84 


18,100 




17,300 


90 


17,100 




17,000 




17,500 




17,000 




15,600 




15.000 


80 


13,400 


65 


12,000 


60 


9,400 




9,300 


73 


8,600 


85 


6,700 


58 


5,000 


100 



Keiiiarks. 



Coma ; recovery. 
September 12th; coma. 
September 13th, eutirely well. 
Coma; recovery. 
Death. 



November 27th ; coma. 

November 29th ; convalescent. 

Recovery. 

Coma: recovery. 

Death. 

Coma; death. 



Coma ; recover}^ 

Temperature, 101°; recovery. 

December 22d. 
December 23d. 



Warthen ^ reports the same condition in a single case. Here 
the specific gravity was also very high (v. Limbeck finds that this 
is to be explained by the increase in the actual size of the cor- 
puscles). 

Other poisons of this class are sidphated hydrogen (H„S) and 
the cyanide compounds. 



^ Vh'chow's Archiv, vol. cxxxvi. 



GENERAL INTOXICATIONS. 



415 



GENERAL INTOXICATIONS. 

I insert here some scattered data on the condition of the blood 
in general systemic or local corrosive poisoning not primarily or di- 
rectly affecting .the blood itself. 

Tansy Poisoning. — A single case examined at the Massachu- 
setts General Hospital showed: Eed cells, 4,600,000; white cells, 
21,000; haemoglobin, 70 per cent. 

Corrosive Foisoning (Ammonia Fumes). — A patient whose 
throat was covered with a fibrinous pseudo-membrane in conse- 
quence of inhaling ammonia fumes showed a leucocytosis of 25,800. 
Red cells and haemoglobin normal. Another with vomiting and 
purging gave a count of 20,700 white cells. 

Table LXXXV. — Ammonia. 



Age. 


Sex. 


Red cells. 


White 
cells. 


Per ceut 
hasmo- 
globin. 


Remarks. 


24 


•• 





27,000 





Mouth and pneumonia. 



Opium Foisoning (Chronic). — The majority of cases of the mor- 
phine habit show normal blood, but in October, 1897, a man of 
twenty-six entered the Massachusetts General Hospital for the mor- 
phine habit who showed at entrance 36,000 leucocytes per cubic 
millimetre. Five days later the count was 21,200. A differential 
count of 500 leucocytes made on this day showed : Polymorphonu- 
clear neutrophiles, 71 per cent; small lymphocytes, 12; large lym- 
phocytes, 10; eosinophiles, 6; myelocytes, 1. At the time of leav- 
ing the hospital he still showed a leucocytosis of 16,400. He had 
no fever, and the physical examination was entirely negative. 

Other cases are tabulated below : 

Table LXXXVI.— Opium. 

Acute Poisoning. 



No. 


Age. 


Red cells. 


White 

cells. 


Per cent 
haemo- 
globin. 

95 
70 
95 

? 

95 
90 
90 


Remarks. 


1 
2 
3 
4 
5 
6 
7 


35 
26 

27 
32 
21 
20 
62 





18,000 
16,000 
13,200 
13,000 
12.000 
10,000 
4,800 


Morphine ten grains. 

Temp. 99.9° ; laudanmn one ounce. 

Opium; melancholia. 

Temp. 101.6°; laudanum. 

Laudanum. 



416 



SPECIAL PATHOLOGY OF THE BLOOD. 

Chronic Poimninfj. 



No. 


Affe. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 
2 
3 


63 
31 
36 




18,200 
13,300 
12,800 


75 

80 
95 




Table LXXXVIL— Poisoning, Acute. 
Chloral. 


No. 


Age. 


Red cells. 


White 

cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 
2 


19 





16,800 
14,400 


100 
54 




Caustic Potcifih. 



J2 mos. 



27,600 


90 


17,000 




22,000 





July 6th. 
July 8th. 
Jufy 11th. 









Corrosire Sublima ti. 






64 




27,200 
16,200 
21.600 
54,600 
42.400 


100 


October 6th. 
October 12th. 
October 13th. 
October 14th. 
October 15th. 


Autopsy. 



Belladonna. 



48 



17,000 



95 



Xitric Acid. 



30 



12,000 
30.200 



90 
100 



Smoke Suffoccitioji 



22 



4 


42 


5 


12 


6 


30 


7 


42 



4,924,000 



23,800 


75 


8,000 




19,100 


89 


19,000 


95 


16.500 


45 


13,000 


63 


10,500 


70 


8.600 


67 



November 5th. 
November 6th. 
Temperature 99.5' 
Temperature 99.9" 



ACUTE ALCHOLISM. 



417 



Ptomain Poisoning (Eotteu Fish).— A mother and her four chil- 
dren were brought to the Massachusetts General Hospital suffering 
from the effects of decayed fish eaten that day. The blood showed 
the following: (1) 3Iother: leucocytes, 21,600, of which 95.3 per 
cent were polymorphonuclear; (2) boy of seven years: leucocytes, 
19,900; (3) boy of three years: leucocytes, 56,800, of which 92 
per cent were polymorphonuclear ; (4) girl of five years : leucocytes, 
32,600; (5) girl of thirteen months : leucocytes, 55,400. The red 
cells and haemoglobin were normal. All the patients made prompt 
recoveries. 

Table LXXXVIII.— Corrosive Poisoning. 
Carbolic Acid. 



i 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 
2 
3 


29 
27 
23 





26,400 
10,300 
15,200 


85 j 
.... No signs. 

1 



Arsenic. 



66 






11,600 




27 






14,000 
18,000 
20,000 
21,500 


80 


20 






16,000 


75 


10 






24,200 
10,200 


75 



March 17th. 
March 20th. 
March 23d. 
March 26th. 

July 3(1. 
July 10th. 



ACUTE ALCOHOLISM. 

Pieraccini (loc. cit., p. 229) in three cases of alcoholic coma re- 
cords the following differential counts : 



Case. 


Polynuclears. 


Lymphocytes. 


Eosinophil es. 


1 


61.8 per cent. 

88.4 
59.7 


36.5 per cent. 

10.8 

30.6 


1.7 per cent. 

.8 " 


2 


3 


9.7 







Achard and Loeper (loc. cit.) in four cases of acute alcoholism 
found " leucocytosis with polynucleosis " ; in twenty chronic cases 
nothing abnormal. 

27 



418 



SPECIAL PATHOLOGY OF THE BLOOD. 



It has been shown experimentally that in animals made drunk 
with alcohol, there is an invasion of the blood and tissues by micro- 
organisms from the intestine. It may be that some of the counts 
here recorded are thus to be explained. 

Table LXXXIX. — Acute Alcohotjsm. 



6 


Age. 


Sex. 


z 






1 


31 




2 


27 




3 


50 




4 


35 




5 


31 




6 


59 




7 


43 




8 


32 




9 


36 


F. 


10 


36 




11 


38 


M. 


12 


43 




13 


42 


M. 


14 


42 




15 


60 




16 


27 




17 


27 




18 


35 




19 


38 




20 


25 




21 


46 




22 


43 




23 


32 


M. 


24 


44 


M. 


25 


48 




26 


48 




27 


60 




28 


29 


F. 


29 


37 


M. 


30 


60 


F. 


31 


30 




32 


32 


M. 


38 


28 


M. 



Red cells. 



White 
cells. 



Per cent 
haemo- 
globin. 



Remarks. 



3,936,000 



4,288,000 



44,000 
32.000 
20,000 
42,000 
29,800 
25.000 
23,900 
22,000 
10,200 
20,900 
18.200 
16,200 
15,900 



14,400 
14,200 
14,100 
12,000 

12,600 

12,600 

12,000 

12,900 

11,200 

11.000 

11,000 

11,000 

10,200 

10,400 

10,200 

9,600 

8,100 

9,200 

8,500 

8,000 

8,000 

7,800 

7,450 

7,000 

11,900 

6,800 

6,400 

7,000 

5,700 

5,600 

5,600 



95 



80 

75 
75 
90 



95 
74 
80 
62 



.0 

90 
65 
95 

85 
80 



85 

30? 

80 

95 
90 
80 
55 
62 
65 



80 
68 



November 1st. 
Xovember 2d. 
November 3d. 
Followed by delirium tremens. 

Delirium tremens. Autopsy. 

April 27th. 
\\m\ 28th. 
Death. 



j Two weeks drinking hard; tem- 
perature 102' ; died, delirium tre- 
mens. 

Delirium tremens; death. 

Temperature 101°. 

Temperature 101'; delirium tre- 
mens. 
Chronic case of delirium tremens. 



Delirium tremens. 



Delirium tremens. 



December 21st. 
December 26th. 

Delirium tremens. 

Autopsy. 
Delirium tremens. 



BASOPHILIC GRANULATION OF RED CELLS 
IN LEAD POISONING. 

Stained with Wright's Modification of Leischmann's Stain. 

(Rlicrophotographs by Lewis A. Brown, Clinico-Pathological Laboratory, 
JIass. General Hospital.) 



PLATE G 





No. 1. 



No. 3. 





No. 



No. 4. 





No. 5. 



No. 



1, 2, and 3, Basophilic stippling. 

4, 5, and 6, Ring bodies as seen in anaemic blood. 



PLUMBISM. 
Table XC. — Chronic Alcoholism. 



419 



i. 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
hsemo- 
globin. 


1 

2 
3 
4 
5 

7 
8 
9 


44 
30 
37 

28 
46 
60 
24 
32 






2,668,000 


15,500 
14.200 
9,000 
9,000 
8,100 
8,000 
7,200 
7,000 


80 
75 
100 
60 
80 
80 
80 
95 



Remarks. 



MERCURIAL POISONING. 

Achard and Loeper {loc. clt.) in 2 cases (one with symptoms 
chiefly digestive, the other cutaneous) found leucocytosis with ter- 
minal eosinophilia (8 to 12 per cent). Of 3 cases of chronic mer- 
curial poisoning, 2 showed leucopenia with diminished polynuclears, 
while in the third the conditions were reversed. In an erythema 
due to calomel Bezanqon (Arch. gen. de Med., 1902, p. 743) noted 
eosinophilia (8 to 14 per cent) (see below, page" 508). 

PLUMBISM. 

Among the deleterious effects produced by lead in the human 
body, anaemia is one of the most serious. It is of the type of or- 
dinary symptomatic anaemias except in one particular, to which at- 
tention has recently been called by Grawitz, viz., spotting or stip- 
pling of the red cells wdth fine basophilic granules, which can be 
well seen in smears stained by Wright's method (vide supra, page 
41), or any basic dyes. These basophilic granules are often seen 
in various forms of very severe anaemia, but in plumbism they ap- 
pear even ivhen the ancemia and other symptoms are of a mild type 
or are absent altogether. 

The following table exemplifies the degree of anaemia and leu- 
cocytosis ordinarily seen: 

Table XCT. — Lead Poisoning. 



1 


Age. 


Sex. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 

2 


29 
30 




4,500,000 
3,800,000 


23,400 

22,800 
16.800 


50 

48 


Lead cohc and headache. 
Eighth day. 



420 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table XCL— Lead Poisoning {Continued). 



Age. I Sex. 



Red cells. 



White 
cells. 



Per cent 
liiemo- 
globln. 



Remarks 



29 
21 



6j 40 



21 
28 
44 
39 
35 
17 
38 
32 
52 



33 

44 
87 

40 



5,130,000 



3,888,000 

3,'700,b00 
3.820.000 
4.258.000 
8.208.000 
4,221.000 



4,000.000 
3,056,000 



22.700 
21,000 
14,800 
14,600 
11.400 



12.600 

11,700 

11.600 

11.000 

10.000 

9,200 

s,600 

7.200 

7.100 



4,848 000 8.000 



5.200 
5,200 
4.800 
4,500 



64 
75 
59 



72 
65 

38 
70 
50 
48 
55 
50 
45 



50 



50 

45 

100 



December 28th. 

February 2d. Polynuclear, 71.2 

per cent; lymphocytes, 24.6; 

eosinophiles, 4; myelocytes, 2. 



Fits, colic, anaemia. 



Colic. 
Chronic. 



August 10th. Polynuclear. 72.4 
per cent; lymphocytes, 23.3: 
eosinophiles. 2.5; myelocytes, 
1.8: megaloblasts, 1: normo- 
blasts. 1. 

August 20th. Polynuclear. 71.4 
per cent: lymphocytes. 25.6: 
eosinophiles. 2.6: myelocytes, 4: 
normoblasts. 1. 



L. X. Boston {FhU. Med. Jour., September 27th, 1902) has 
called attention especially to the leucocyto.^is which occurs in plumb- 
ism. He presents the following data: 









c 




7' r 


X 


: 








-2 






£- 


c •' 




Red cells. 


White 
cells. 


^1 

^ 5 




25^55 


l| It. 


£ 


^3 Remarks. 


^ 






B. 


i 


B 


S-. 


' % £ 


2 




1 


3,335,000 


14,000 


60 


68.5 


16.5 


10.5 


0.5 


4.0 


1 


1 


400 whites counted; colic; blue 
line. 




3,100,000 


15,200 


68 


64.5 


20.5 


10.5 


3.0 


1.5 






Eiffhteen davs later. 


'Z 


2,930,000 


8,000 


50 


62.5 


26.5 


8.0 


2.512.5 


4 


:o 


400 whites counted ; colic ; blue 
line; paralysis. 


'6 


4,940,000 


20,800 


87 


88.5 


\ .0 


2.0 


.o;2.o 








Paralysis ; blue line ; died twenty- 
four hours later. 


4 


5,500,000 


11.200 


79 


71.5 


21 .5 


6.0 


1.0 


.0 








Colic ; blue line. 


rt 


3.810,000 


13.200 


32 


65.5 


21.0 


9.0 


3.0 


1.0 








Delirium ; blue line ; tremor. 


6 


5.090,000 


7,200 


87 


48.0 


40.0 


8.5 


2.5 


1.0 





2 


400 whites counted ; colic (mild>. 


7 


3,700.000 


7,000 


37 


63.0 


28.5 


6.5 


.02.0 


4 


1 


200 whites counted : no symptoms. 


8 


2,770,000 


4,000 


51 


60.0 


30.0 


5.5 


.54.0 


4 





400 whites counted ; debility ; blue 
line. 


y 


4,760,000 


25;500 


46 


58.0 


33.0 


4.7 


1.03.28 


4 


1 


400 whites counted. 



SUNSTKOKE AND HEAT EXHAUSTION. 



421 



During the colic various writers {e.g.^ Becker ') have uoted leu- 
cocytosis — 19,000 or more. 

SUNSTROKE AXD HEAT EXHAUSTION. 

The leucocyte count may be either high or normal, according to 
conditions not well understood. 

Table XCH. — Sunstroke. 



i 

1 






Per cent 




6 1 ^ge. 


Red cells. 


White cells. 


haemo- 


Remarks. 


2 








globin. 




1 


10 




24,000 
13,400 


67 


Two days later. 


2 


35 




22.800 




Temp. 107^ Died. 


3 


45 




21.000 






4 


46 




19,400 


98 


Temp. 109'. 


5 


60 





14,300 


83 


Temp. 106°. 


6 


49 




13,600 


70 


Temp. 110'. Delirium tremens. 


7 


48 




13.000 


70 


Temp. 110.5'. Dehrium tremens. 
Death. 


8 


64 





11,500 


70 


Temp. 109 \ 


9! 23 




10,000 
5,200 




Temp. 110°, first dav. 

Temp. 104', fourth dav. Died. 


10 47 




10,000 


95 




11! 50 




10.000 






12i 32 




9,800 


62 




13! 44 




9.200 


95 


Temp. 105°. Delirium tremens. 












Death. 


14 


30 




9.000 


9 


Temp. 103°. 


15 


28 




8,200 


62 


Temp. 107°. Delirium tremens. 
Death. 



Lambert (Loomis-Thompson " System of Med.," vol. iii., p. 876) 
found in 12 cases of sunstroke haemoglobin values from 85 to 125 
per cent, and a leucocytosis. 

Lewis and Packard (^Am. Jour. Med. Sciences, 1902, p. 406) ex- 
amined 17 cases of sunstroke. '" All but 3 of the severe cases had a 
leucocytosis at some time, but tliere was considerable irregularity in 
the time and duration of the rise. The increase was usually in the 
polynuclear cells " (94.8 per cent, 89.2 per cent) with absence of 
eosinophiles. 

Table XCHL— Heat Exhaustion. 



^ 


Age. 


^ RM cells. 


White cells. 


Per cent 
h£emo- 
globin. 


Remarks. 


1 

2 
3 


20 
62 





24,000 
19,800 
18,200 


80 
95 


Recovery. 
Recovery. 


Temperature 98.8°. 



422 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XCIII. — Hp:at Exhaustion {Continued). 



6 


Age. 


Red cells. 


White cells. 


Per cent 
haemo- 
globin. 


Remarks. 


4 
5 

6 
■7 
8 
9 
10 
11 
12 


34 

54 
30 
32 
15 
60 
48 
37 


........ 


11,000 
9,000 
5,000 
8,800 
7,600 
6,200 
5,400 
5,000 
5,400 
4,450 


75 

85 
90 
95 
80 
85 
73 
61 


Recovery. 

Recovery. Temperature 98^ 

Recovery. Temperature 99'. 
Temperature 97", 

Temperature 96'. 
Temperature 99.6.° 



Age. 
25. 



Electric Shock. 



White cells. 
. . 8,900 



PART VI. 

MALIGNANT DISEASE, BLOOD PARASITES, 
AND INTESTINAL PARASITES. 



CHAPTER X. 

MALIGNANT DISEASE. 
The Blood as a Whole. 

1. The specific gravity is reduced in most cases, running roughly 
parallel with the haemoglobin. 

2. Coagulation is normal or slower than normal in uncompli- 
cated cases. When sloughing and inflammation are present it may 
be rapid, 

3. Fibrin is usually normal; an increase means inflammation in 
or around the tumor or an inflammatory complication. 

4. Occasionally the resistance of the red cells is extraordinarily 
low. In one of my cases the ordinary manipulations of preparing 
specimens (either fresh or film) for examination invariably mangled 
the red cells beyond recognition, no matter how quickly and care- 
fully the technique was carried out. In the fresh specimen the 
red cells seemed to fuse into each other in clumps, their bieoncavity 
lost. The plasma became turbid with haemoglobin despite every 
precaution. 

This was a case of cancer of the kidney with multiple hemor- 
rhage from various surfaces. I have never seen another case like 
this one, but in literature several such are mentioned. 

CANCER. 

Red Corpuscles. 

As in tuberculosis, we are frequently surprised to find but little 
diminution in the number of red cells. In all but very advanced 
cases this is the rule. It is a chani^e of the individual red cells 



424 



SPECIAL PATHOLOGY OF THE BLOOD. 



(pallor, loss of size, of weight, degenerative changes;, rather than a 
reduction of numbers. 

Nevertheless in the later cachectic stages of most cases of malig- 
nant disease, we do find a quantitative anaemia, the counts often 
running as low as 2,500,000 and occasionally sinking as low as in 
pernicious anaemia. Thus v. Limbeck records a case (complicated 
by repeated hemorrhages) with only 950,000 red cells jjer cubic 
millimetre, and Prese * cases with 800,000 and 681,000 respectively. 
The lowest count in my own cases was 1,457,000. 

There seems to be no consideral)le difference between cancer and 
sarcoma as regards their effects on the red cells. 

The count of red cells is sometimes above normal, doubtless due 
to concentration of the blood from some cause. Probably the same 
influence is at work in other cases, and many of those showing nor- 
mal counts have really fewer red cells than they should. Such ab- 
normally high counts are not rare, as the following examples show : 



Author. 


Case. 


Aflff.ction. 


Red ceUs. 


Per cent 
haemoglobin. 


Osterspey- . . . 

Osterspey 

Osterspey 

Neubert^ 


1 
3 
3 
1 
2 


Cancer of the stomach 


5,040,000 
6,184,000 
8,280,000 
5,085,000 
4,918,000 
6,200,000 


80 


Cancer of the liver and stomach 
Cancer of the gullet 


87 
48 


Cancer of the stomach 


73 


Neubert 


Cancer of tlie liver . 


70 


Reinert-^ 


Cancer of the stomach 


77 



I wish to lay some stress upon this point, because it has been 
stated by some recent writers (e.y., Grawitz: "Pathologic des 
Blutes," Berlin, 1896) that the red cells are almost always dimin- 
ished in malignant disease. 

The high counts in cancer of the gullet are obviously to be ex- 
plained by the lack of liquid taken, the blood being greatly concen- 
trated as in any other form of starvation. 

That this increase is not invariably present (see Table XCVIII., 
page 439) is doubtless because some oesophageal tumors permit the 
ingestion of liquid in normal amounts and of a certain amount of 
solids. In gastric cancer high counts are usually due to concentra- 
tion of the blood produced by vomiting or to the lack of absorption 
of fluid accumulating in a dilated stomach with pyloric obstruction. 

'Frese: Deutsch. Arch. f. klin. Med., v(3l. 68. 
-Dissert., Berlin, 1892. ^i^aug. -Dissert., Dorpat, 1889. 

^ "Zahlungd. Blmkorp.." Leipzig. 1891. 



CANCER. 



425 



The highest counts in the Massachusetts General Hospital series 
are in simple gastric cancer without any stenosis at either end of 
the organs, and the lowest count (1,632,000) was in a similar case 
just before death. 

Hcenioglohin. 

Bierfreund,' who has examined 72 cases with regard to their 
percentage of coloring matter, found that in relatively slow and 
long-standing cases it averaged 68.5 per cent, and in the worst 
cases 57.5 per cent. In cases of mammary cancer after operation 
the haemoglobin is of course lower owing to hemorrhage, and Bier- 
freund noticed that as a rule the hsemoglobin began to rise toward 
normal much later than after operations for non-malignant condi- 
tions — a week later on the average— tn^f/ that it never reached the 
jjoint at ichich it ivas before the ojyeration.' 

The following table from Bierfreund is of interest as illustrating 
these points. Cases were examined before and after operation, and 
the examinations were continued daity after the operation until the 
haemoglobin began to rise again. This occurred very late as com- 
pared with other operations. 



Diagnosis. 


Per cent 

haemoglobin 

before 

operation. 


Per cent 

haemoglobin 

after 

operation. 


Per cent 
loss. 


Regeneration time. 


Malignant tumor without 
complication. 

Very large or rapidly grow- 
ing tumors. 

Tumors with "softening" or 
disturbances of function. 


68.5 
56.6 
57.5 


53 

38.4 
39.7 


15.5 

18.2 
17.8 


23 days. 
27.8 days. 
27 days. 


Total, 72 cases. 


Av. , 60 


A v., 42.8 


17.2 


Av., 25. 9 days. 



By " regeneration time " is meant the number of days elapsed 
after operation before the haemoglobin begins to rise. After opera- 
tions for other causes (non-malignant) the average regeneration time 
is from fourteen to twenty days. 

^ Langenbecli's Archiv, vol. xH. 

^ This is all the more extraordinary because Bierfreund specially noted that 
even in patients who gained weight notably after the operation the hsemoglo 
bin did not rise so high as it had been before operation ; he watched them lor 
months after it. Apparently the actual presence of the tumors is not the only 
cause of the lack of corpuscle substance. 



426 SPECIAL PATHOLOGY OF THE BLOOD. 

It is very important that these results of Bierfreund's should be 
tested. In Mikulicz's surgical clinic at Breslau all patients have 
their haemoglobin tested regularly. Osier and McCrae in 52 cases 
of gastric cancer record an average of 49.9 per cent of haemoglobin 
— a color index of 0.63. Their readings were: 

Case.s. Cases. 

80 per cent or more 3 40 to 50 8 

TO to 80 7 j 30 " 40 14 

60 " 70 6 I 20 " 30 7 

50 " 60 5 Below 20 2 

Reinbach ' examined 16 cases and found the haemoglobin range 
between 18 to 70 per cent, with an average of 50 per cent. 

Rieder's^ cases average 53 per cent (sarcoma much lower — see 
below) . 

Laker ^ noticed the low haemoglobin percentage in malignant 
tumors and thought it a help in excluding benign tumors or tuber- 
culosis, in which the htemoglobin is much less diminished. 

In the 87 cases of malignant tumors in which I have notes of 
the haemoglobin (see tables) the average is 58 per cent. Comparing 
this with the average count of red cells (4,140,000), we get a color 
index of 65, distinctly higher than the average of chlorotic cases, 
of wliich, however, the figures distinctly remind us. The highest 
cases of this series had 100 per cent and 90 per cent of haemoglobin 
respectively, and the lowest 20 per cent and 22 per cent; in these 
last two cases the color indexes were 0.36 and 0.58 respectively, not 
excessively low. As pointed out by Taylor (loc. cit.), cases of ma- 
lignant disease can be divided into three groups with reference to 
their blood. 

1. Those with approximately normal blood. 

2 Those with a low haemoglobin but a nearly normal number of 
cells 

3. Those with great diminution both in cells and coloring matter. 

Among our own cases at the Massachusetts General Hospital 
about one-half fall under the second group, one-quarter under the 
first, and one-quarter under the third. 

As the disease progresses, the red cells and haemoglobin steadily 
go down (except in cancer of the gullet), and at the time of death 

^ Langenbeck's Archiv, 1893, p. 486. 

^ "Beitrage z. Kenntniss d. Leiicocytosis," Leipzig, 1892 (Vogel). 

3Wien, med. Woch., 1886, Kos. 18 and 19. 



CANCER. 427 

1,000,000 cells per cubic millimetre is not rare. It is very rare to 
find the red cells reduced below 1,000,000, much rarer than in per- 
nicious anaemia. Improvement under treatment is rare in cancer, 
common in pernicious anaemia. This is important in diagnosis. 

The color index usually remains below 1. Compared to most 
other varieties of secondary anaemia {e.g., those in tuberculosis or 
nephritis), a quantitative anaemia — that is, a loss of red cells as 
well as of haemoglobin — is relatively more frequent. In general 
the degree of anaemia is parallel to the amount of cachexia, except 
when hemorrhage increases it (as in tumors of the stomach or 
uterus). 

How far the anaemia may be due to actual destruction of cells 
b}^ toxic (?) products of the tumors is doubtful, Grawitz found 
that the injection of extracts of cancerous tissues caused in rabbits 
a temporary dilution of the blood, so that the cells per cubic milli- 
metre were diminished, and it may be that this plays some part in 
the causation of the low blood counts. 

Qualitative Changes. 

{a) The average diameter of the red cells is often diminished 
either as in chlorosis by a diminution in the size of nearl}' every 
corpuscle, or by a less general shrinkage, many cells being of nor- 
mal size. The very large forms seen in pernicious anaemia are rare 
in the anaemia of malignant disease, and never, I think, reach the 
size of the giant forms seen in the former condition. Very small 
cells, on the other hand, are as common in advanced cases as in any 
other form of anaemia, except chlorosis > Deformities and degenera- 
tive changes are very common in well-marked cases, often as great 
as in pernicious anaemia, though they may be slight or absent. 

According to Strauer, the deformities found in malignant disease 
are greater than those found in any form of tuberculosis, and this 
fact he thinks of value in diagnosis. This observation has been 
confirmed by Taylor. 

Degenerative changes are sometimes well marked, but seldom, if 
ever, reach so extreme a condition as occurs in many cases of per- 
nicious anaemia. 

(J)) Nucleated red corpuscles are the rule in all advanced cases, 
and in some others. Taylor found them in one-half of the twenty- 
two cases examined by him. Malignant disease differs in this re- 



428 SPECIAL PATHOLOGY OF THE BLOOD. 

spect from tuberculosis and most other conditions involving second- 
ary anaemia, in that the nucleated red cells are much more common 
in cancer and may appear even when there is no considerable loss 
of red cells (numerically) or even when the hsemoglobin is also 
normal (Schreiber). I have found them in four-fifths of all severe 
cases examined. 

As a rule the nucleated corpuscles are of tlie normoblast type- 
(including small forms with dividing nuclei), but in very cachectic 
cases we may find megaloblasts as well — always, so far as I know, 
fewer in number than the normoblasts. Osier and McCrae found 
no typical megaloblasts in their 59 cases. The megaloblasts, when 
present, are in the minority as compared with the normoblasts. 
For example : 

C''^^ I- l?l7eeTcTa^btsts. | Seen wlail,. cor.uting 400 Iccocytes. 

c- II. \ s:regrbiir [ *«- -'■"■■ '—"■^' '"« -- 

Case III. I ^^- -rXr [ Seen wLi„. .„„„.,„ 200 cells. 

Cases could easily be multiplied. 

The characteristics of the blood changes in malignant disease, 
then, so far as concerns the red cells, are those of secondary anae- 
mia, which at times attains the severest type — but only when ca- 
chexia is marked or when hemorrhage complicates the disease. 

The specific gravity follows in a general way the haemoglobin 
percentage. 

On the ivhite corpuscles in malignant disease a great deal of in- 
terest has centred, and very conflicting reports have been published. 
As the effects of cancer and sarcoma seem to be somewhat different^ 
we will consider them separately. 

The Leucocytes ix Caxcer. 

Quantitativ e Ch a n ges . 

We should expect great differences in the blood of different cases 
if we consider what a wide range is included between the small, 
hard, slow-growing, curable cancer of the lip which may produce 
little or no impairment of the general health, and the " fulminat- 
ing," rapidly growing cases with numerous metastases and profound 
prostration. 



CANCER. 429 

The former class of cases may show a blood normal in all re- 
spects, while in the latter the blood may be so profoundly altered 
as to be confused with that of pernicious ansemia or of leukaemia. 
Da Costa found leucocytosis in forty-five per cent of cancer cases 
and sixty-five per cent of sarcoma cases. 

In a general way it may be said that the more " malignant " the 
cases the greater the changes in the blood. 

The effect upon the leucocytes depends upon the following con- 
ditions : 

1. The position of the tumor. 

2. Its size, rapidity of growth, and the number, size, and posi- 
tion of its metastases. 

3. The resisting power of the individual. 

1. Position. — (a) Tumors of the gullet involving stricture but 
not extending to other tissues are often accompanied by a dhninu- 
tion of the leucocyte count, owing to the starvation which they pro- 
duce. This is not true of all cases, as is shown in the accompany- 
ing tables, but when the leucocytes are increased there is usually an 
involvement of other organs as well. 

(h) Cancers of the uterus and some of those of the stomach, by 
reason of the hemorrhage which they produce, are apt to be associ- 
ated with a very high leucocyte count. 

(c) Tumors of the thyroid and of the pancreas are said by some 
writers to cause a specially great leucocytosis. In my own experi- 
ence, tumors of the kidney have shown very marked increase of 
white cells. 

2. Size. — Other things being equal, the larger and more rapidly 
growing tumors show in most cases a greater leucocytosis than 
small, slow-growing ones. 

Thus the cancers of the lip and of the pylorus, scirrhus of the 
breast or of the penis, show smaller counts than tumors of the liver, 
omentum, and kidney, which are apt to grow more rapidly. Metas- 
tases in the bone marrow are thought by some observers to give 
peculiar qualitative blood changes (see below). 

In general, metastases, being a method of rapid growth, simply 
add to the leucocyte count. 

These distinctions eliminate some of the apparent contradictions 
between the findings of different individuals who were simply de- 
scribing cancers of different types. But even within a single type, 
there are very marked differences in different cases, For instance, 



430 



SPECIAL PATHOLOGY OF THE BLOOD. 



Alexander ^ found the leucocyte count in cases of scirrhus of the 
breast to vary between 2,360 and 21,700. Similar differences have 
been reported in cancers of the stomach (e>^., Schneider" finding 
leucocytosis in all of twelve cases, while Osterspey ^ in another 
series of twelve cases found leucocytosis in only two). 

3. Resisting Poiver. — Possibl}' a part of these differences is to 
be explained by differences in the resisting power of the individual. 
But if this is so, we cannot measure the endurance of a given pa- 
tient by his general health. As in the Civil War the pale, city- 
bred men outlasted the healthy farmers, so here the tumor's rapidity 
of growth seems often to be greatest in the most vigorous young in- 
dividuals, while dried-up old women will resist its advance for a 
longer period. 

We come now to tlie conditions to be found in particular types 
of cancerous growth. 

Surprisingly little work has been done on the blood in malignant 
disease, such cases usually being under the charge of surgeons who 
rarely value such investigations. Except for scattered counts here 
and there, all our knowledge of the corpuscles rests on the work of 
Hayem and Alexander in France, and Kieder, v. Limbeck, Pee. 
Sadler, Reinbach, Osterspey, Grawitz, Strauer, Schneyer, and 
Schneider in Germany, Cunliffe in England, Da Costa, Taylor, and 
myself in this country. 

Cunliffe's thorough study of seventy-eight cases of cancer {Medi- 
cal Chronicle, September, 1903) is summarized in the table on the 
opposite page. I regret that it came to me too late to be more fully 
utilized in this edition. 

4 

Da Costa summarizes his results in the following: table : 



Seat of Growth. 


No. of 
cases. 


No. and per 

cent with 

leucocytosis. 


Average 
count. 


Maximum 
count. 


Minimum 
count. 


Stomach 


23 

10 

8 
7 
6 


9 or 39 
2 or 20 

4 or 50 

5 or 71 
4 or 66 


8.100 

9.300 

10.700 

14,400 

18,700 


14,000 
24,000 
16,000 
31,500 
40,800 


1.000 


Uterus 


4,500 


Rectum 


6,^0 


Breast 


8,000 


Liver 


8.000 







^ Alexander : These de Paris, 1887. 
-Inaug. -Dissert., Berlin, 1888. 
3 Inaug. -Dissert., Berlin. 1892. 



CANCER. 



431 





> d w H 


W 


9 


GD 1 






li 




ongue . . 
reast .... 

terus . . . 
bdomen . 




cT 


O 

3 

1 


1 ! 


3^1 


-5 OD QC to 


O 


1—^ 

CO 


o 


No. of cases. 






*" pi p 


px 


p 


pi 










00 OT o 


to 


to 


"co 










CO wT -3 

O O O 


o 


OD 

o 


§ 


Highest count. 








"o o o 


~J^ 


(^ 


■^ 










o o o 


o 


o 


o 










O "O o 


o 


o 


o 










i^ S^ Jp5 


pa 


OS 


to 








Crj CO "-5 


^_i 


Of 


OS 




a 








P 


8 


p 


Lowest count. 


c:^ 

ft) 






O O O 


(^ 


(^ 


^ 










O O O 


^ 


1^ 


<3> 




tj* 




■ O O O 


o 


o 


o 








CO *- i*^ *- 


*- 


4^ 


4^ 






O O Or ~CO 


CO 


"bo 


<J 








O CO Oi *^ 
J^ P p p 


o 


M 


J^ 


Average count. 






^o ^> ^s o> 


^) 


^^ 


~^ 








o o o o 


^ 


o 


§ 








o o o o 


o 


o 








. 




1— t 






w 






^ : S 


^ 


Ol 


^ 


Highest. 


ill 




to • . OS 

OS • o 


^ 


Or 

4^ 


s 


Lowest. 




4^ rfi' • -^ -<{ 
GO O O fji^ 


--3 


00 


::! 


Average. 






to to H-t 


to 


t-i 


CO 








9 r5 o 


Q 


o 


Q 










P 


p 


p 


Normoblasts. 






O O O 


CD 


o 


CD 








O! 02 


CQ 




OD 








or CO to 


to 


CO 


CO. 




1 






P 5^ ^^ 


P 


p 


p 










to rfi. 00 


"to 




oo 


Highest count. 












(^ 


o 










*. o o o 


o 


o 


o 




IS 
























l_l 






a 






-1 :^ -5 


p 


p 


p 




2 






O rf^ 00 


00 


o 


"to 


Lowest count. 


o 
d 






o o o 


o 




o 




Ki 




: o o o 


o 


o 


o 




3 




lO ^ ^ 


^_^ 


J_^ 


l_^ 






CO to h-^ cc 


i^ 


CO 


J<I 








"h^ 00 rfi^ V 


"•<? 


"-3 


to 


Average count. 




. 


o o o o 


■00 




oo 








o o o o 


o 


<^ 


o 








>— 1 1— 1 ^ 1— 1 


o 


B 








SJ-aooooBOcoooH^on 


^ o 


creased 
of 13 c 
Over 8 








reascd. 
reased i 
2 cases, 
f 8 wit 
c y t 
ho w e 
rease of 
uclears. 
reased i 
cases, 
reased i] 
cases (8 
4, 74). 


ent in 

82, 8 

80, 7 

lers n 


-5 00 00 


if 




C 00 H-^ >f=- 


*^J*^P 


^ 






P 


OP g- 

'^ CD 




•^i 




t-LO O ^B^S O 


B p 


CD 00 ^^ 








-i Ms Ms . T JO 1 i-fs 




-- • I—' 










o 


'^ < i-i 






■^ 






o 






B 






o 
^ 


^^g 






w 




















■ 8 


^'o| 






<<i 








>— 1 p 






e?- 






po 


s 1 -• 






^ 




CO 




Ol 




W 




H-.bo 




^'^ 




S 




p 




CD 








►rJ 




O i-J 




e 








is 




G 






i 


B 




B 

b' 




1 







432 SPECIAL PATHOLOGY OF THE BLOOD. 



CANCER OF THE BREAST. 

Most of our data came from Hayem ' and his pupil Alexander.' 

1. Scirrhus Growths. — Number of cases, 14. Average leuco- 
cyte count, 11,400. Highest count, 21,700; lowest, 2,360— the 
last is somewhat doubtful as to diagnosis; except for this case, 
which was in a very old, dried-up woman, the lowest count was 
7,400. 

In 10 out of the 14 cases, the count was over 10,000. In the 3 
cases seen by the writer 2 showed no leucocytosis, 1 a considerable 
leucocytosis. 

2. MeduUai'u {Eacephaloid) Growths. —Three cases, all over 
10,000— average 11,300. 

Houston (Brit. Med. Journ., November 14th, 1903) reports a 
case of cancer of the breast complicated by many hemorrhages from 
mucous membranes and under the skin. Repeated blood examiaa- 
tions showed figures like the following: Red cells, 1,600,000; 
haemoglobin, 33 per cent (color index, 1.03); leucocytes, 6,000. 

Differential count of 500 leucocytes showed: Polynuclears, 
56.4 per cent; lymphocytes, 38.3; large mononuclears, 5.2; eosin- 
ophiles, 0. 

Twenty-seven megaloblasts and thirteen normoblasts were found 
during this count. At autopsy metastatic cancerous nodes were 
found in the marrow. The blood, as will be seen, is that of per- 
nicious anaemia. 

Effects of Operation. 

The following figures from Hayem are also of interest: 

Case I. — Scirrhus of the Breast. 

Before operation 21,700 

Five weeks after operation (wound not 

quite healed) 10,000 

Wound completely healed 6,200 

Seven months after operation 8,990 (beginning to rise again). 

The growth recurred some months later and leucocytosis was again present. 

^ Hayem: "Du Sang," Paris, 1889, p. 947. 

2 G. Alexander: "De la Leucocytosis dans les Cancers," Paris Thesis, 1887 



CANCER OF THE STOMACH. 433 

Case II. — Scirrhus of the Breast. 

First Second 

count. count. 

Before operation 11,500 11,450 

After operation 8,500 6,200 

Case III. — Scirrhus of the Breast. 

First Second 

count. count. 

Before operation 11,000 13,400 

After operation 8,400 

Case IV. — Scirrhus of the Breast. 

Before operation 7,400 

After operation 1,300 

Case V. — Medullary Cancer of the Breast. 

Before operation 10,000 

After operation 9,000 

Hayem considers that by watching the leucocyte count we can 
predict the coming of a recurrence before any physical signs are 
present. This he did in Case I. of the series just given. 

I have seen no confirmation or refutation of this statement. It 
is one of the many points to which the attention of surgeons should 
be directed. 

CANCER OF THE STOMACH. 

Taking all the cases of cancer in my series together, the average 
of the 129 at the time when treatment began ivas 4^018,000 red cells 
per cubic viillimetre. 

In Osier and McCrae's 59 cases the average red count was 
3,712,186 per cubic millimetre. Their counts ranged: 

Over 6,000,000 3 cases. 

5,000,000 to 6,000,000 7 " 

4,000,000 " 6,000,000 17 " 

3,000,000 " 4,000,000 16 « 

2,000,000 " 3,000,000 8 " 

1,000,000 " 2,000,000 8 " 

Table XCIV.— Gastric Cancer at the Massachusetts Hospital. 

Red cells. 

Between 1,000,000 and 2,000,000 6 cases. 

2,000,000 " 3,000,000 20 " 

28 



434 SPECIAL PATHOLOGY OF THE BLOOD. 

Red ceUs. 

Between 3,000,000 and 4,000,000 44 cases 

" 4,000,000 " 5,000,000 32 " 

5,000,000 " 6,000,000 23 " 

Over 6,000,000 4 " 

Average, 4,000,000 - 129 cases. 

Nucleated red cells present in 11 cases out of 114 examined. Normoblasts 
always in majority. A few megaloblasts in 3 cases. 

Table XCV. — Gastkic Cancer. 

Leucwytes per cubic inilliuietre. 

Between 3,000 and 4,000 3 cases 

4,000 " 5,000 12 "" 

5,000 •' 6,000 26 " 

6,000 " 7,000 26 " 

7,000 " 8,000 19 " 

8,000 " 9,000 20 " 

" 9,000 " 10,000 26 " 

10,000 " 12,000 34 " 

12,000 " 15.000 27 " 

15,000 " 20,000 28 " 

20,000 " 30,000 9 " 

30,000 " 40,000 5 " 

Total, 372 counts in 235 cases.' 
Average, 10,600 + 

Hayem'- in 12 cases found leucocytosis present in o, absent 
in 7. 

Schneider' in 12 cases found leucocytosis in 12 (all). 

Schne3^er ' in 18 cases found leucocytosis in 4, and these 4 all 
under 11,000. 

Osterspey ' in 12 cases found leucocytosis in 5. 

Eieder ° in 6 cases found leucocytosis in 3. 

Sadler ® in 13 cases found leucocytosis in 2, and in both there 
were complications (abscess of liver, perforation of gullet with gan- 
grene) to which the leucocytosis might be due. 

1 Where several counts were made in one case tiiey are here averaged and 
counted as one case. 

2 "Du Sang," Paris, 1889, p. 948. ^ Inaug. -Dissert., Berlin, 1888. 
*Inaug. -Dissert., Berlin, 1892. ^ Loc. cit. 

^ "Oriffinal-Mittheilunffen aus der Klinik v. Jaksch." 1891. 



CANCER OF THE STOMACH. 435 

Eeinbacli ' in 4 cases found leucocytosis in 2. 

Reinert '^ in 2 cases found leucocytosis in 2. 

Laache ' in 5 cases found leucocytosis in none." 

Despite these facts we have the record of a certain number of 
single cases in which the leucocytosis has been enormous For in- 
stance, Welch in Pepper's " System of Medicine " mentioned a 
case in which the ratio of white to red cells was 1 : 25 (normally 
1:750 + ). 

Eisenlohr's ^ case showed 1 white to 50 red, and Potain's ® case 
showed 1 white to 48 red cells. 

The Massachusetts General Hospital series of 235 cases showed 
leucocytosis in 69 cases and none in 176 (see Table XCV.). Out 
of those showing leucocytosis 27 were under 15,000, that is, the 
leucocytes were but slightly increased, leaving only 42 out of 235 
(or 18 per cent) in which the leucocytosis was very marked. Among- 
these 20, the highest counts -vVere 40,000 and 39,000, and the 
highest ratio 1 : 62. 

From this series I have excluded all cases in which there was evi- 
dence of metastasis in other organs; this means excluding 19 cases, 
11 of which showed leucocytosis, and helps to account for the low 
average leucocyte count in the other 235 cases. 

In over three-fourths of these cases the diagnosis was made cer- 
tain either by operation or by autopsy ; all the others showed either 
a palpable tumor in old cachectic patients with pain and vomiting, 
or other equally clear evidence for the diagnosis. Doubtful cases 
have been excluded. As Avill be seen by the table, in some of the 
cases the counts were verified by repeated examinations, while in 
others only a single count — that made when the patient entered the 
hospital — was recorded. 

As a rule, the high leucocyte counts were in the more cachectic 
cases; but this does not always hold. Three cases in Table XCIV. 
were very cachectic but showed no leucocytosis. 

The position of the tumor in one or another part of the stomach 
seemed to have no connection with the number of leucocytes. Osier 

^ Langenbeck's Arcliiv, 1893, p. 486. ^ Loc. cit. 

^"Die Anamie," Christiania, 1883. 

^ Apparently, since he draws attention to the fact that there is leucocytosis 
in a case of cancer of the uterus. 

= Deut. Arch. f. klin. Med., 1877, vol. xx. 
«Gaz. desHop., 1888, Xo. 57. 



436 SPECIAL PATHOLOGY OF THE BLOOD. 

and McCrae ' found no leucocytosis in 29 cases out of Gl\ Their 
counts showed : 

Leucocytes. 

Below 5,000 14 cases. 

5,000 to 8.00(» 15 - 

8,000" 12,000 15 " 

12,000 " 20,000 15 '• 

20,000 '' 30,000 3 " 

62 cases. 

Their highest count, 28,000, was in a case with extensive hepatic 
metastasis. The number seemed to bear no fixed relation to the 
situation of the growth, nor to the amount of ulceration, of metasta- 
sis, or of fever. 

On the whole we get, I think, very little information of any diag- 
nostic value from blood counts in gastric cancer. Leucocytosis is rela- 
tively infrequent in cancer of the stomach, occurring in only about 
one-fifth of the early cases. As the disease progresses we may get 
a leucocytosis, particularly in case its growth is rajyid and metastastes 
are frequent and numerous; but some cases, particularly those in 
which the tumor is small and grows slowly, may run their entire 
course without any leucocytosis being present. In this respect they 
are like the majority of small, slow-growing cancers in other parts 
of the body (see below). 

Hemorrhage or perforation is of course accompanied b}^ an in- 
crease in the number of Avhite cells — in fact the highest count in 
the present series (105.600) occurred in a case in which a cancer of 
the stomach with metastases in the liver perforated into the perito- 
neal cavity and started a virulent, quickly fatal peritonitis. 

DIGESTION LEUCOCYTOSIS IN CANCER OF THE STOMACH. 

A considerable body of statistics has accumulated to show that 
in the great majority of cases of gastric cancer the leucocytosis of 
digestion (see page 91) does not occur. R. Miiller ^ noticed this 
fact in 5 cases of cancer of the stomach. Schneyer ^ in 18 cases 
found it invariably absent, while in 3 cases of benign stenosis of 
the pylorus a considerable digestion leucocytosis appeared, as was 

1 Osier aud McCrae: N. Y. Med. Jour., May 19th, 1900. 
2Prag. med. Woch., 1890, No. 17. 
s^eit f. kiln. Med., 1895. p. 475. 



LEUCOCYTOSIS IN CANCER OF THE STOMACH. 437 

also tjfe^rpjase ill P^iit of 8 cases of ulcer of the stomacli, tlie excep- 
tion being a fatal case. 

He found both incipient and advanced cases to be similarly 
affected. In 5 of his cases and in some of Mtiller's HCl was pres- 
ent in the gastric contents, so that the absence of digestion leucocy- 
tosis was not due to absence of HCl. 

Hartung ' in a series of 10 cases (mostly advanced) found no di- 
gestion leucocytosis, whereas a marked increase occurred in cases of 
malignant disease of other organs. Osier and McCrae found no di- 
gestion leucocytosis in 12 out of 22 cases. 

Capps ^ in 17 cases examined at the ^lassachusetts General Hos- 
pital found a digestion leucocytosis in 2, the increase being respec- 
tively 3,270 and 3,850 cells over the count before the beginning of 
digestion. In the other 15 cases there was no increase after a large 
proteid meal. Since Dr. Capps' article 20 more cases have been 
investigated at the hospital, in 19 of which the digestion leucocyto- 
sis was absent. Thus in a total of 37 cases only 3, or 8 per cent, 
showed any digestion leucocytosis. In 5 out of 10 cases of chronic 
gastric catarrh the digestion leucocytosis was present; it was also 
present in a case of benign stricture of the pylorus in a man of 
forty-nine on whom an operation was successfully performed later. 
The digestion leucocytosis may, however, be absent in various gas- 
tric diseases and in simple debility and has been shown by Eeiiki ^ 
and others to be subjected to the normal function of the pylorus 
and of the bowels. Out of 144 cases tabulated from various authors 
by Da Costa, 119, or 82 per cent, had no digestion leucocytosis. 

On the whole subject of the blood in gastric cancer I agree in the 
main with the conclusions of Osier and McCrae (loc. cit.) : 

"1. In a doubtful case a blood count below 1,000,000 red cells 
per cubic millimetre is strongly in favor of pernicious anaemia. 

" 2. While nucleated red corpuscles occur in all very severe anae- 
mias, megaloblasts rarely if ever appear in cancer of the stomach. 

" 3. Neither an increase in the leucocytes nor special variation in 
the different forms appears to be of any moment in the diagnosis of 
gastric cancer. 

" 4. The presence or absence of digestion leucocytosis is too un- 
certain to be of much assistaiice in diagnosis." 

1 Wiener klin. Woch., p. 697. 1895. 

2 Boston Med. and Surg. Journal, November 4th, 1897. 
^Renki: Arch. f. Verdauungskr. , 1901, vol. vii. 



438 



SPECIAL PATHOLOGY OF THE BLOOD. 



CANCER OF THE STOMACH WITH METASTASES. 

Most writers have not separated the cases with metastasis from 
those without it. A glance at the nineteen cases of Table XT' VI. 
shows that with four exceptions leucocytosis was present throughout 
most of the disease. 





Table XC VI.— Cancer of 


THE Stomach with Metastases. 












Per cent 




Q 


Age. 


Sex. 


Red cells. 


White cells. 


haemo- 


Remarks. 


z 










globin. 




1 


54 


•• 


5,539,000 


3,900 a.c. 
4,200 p.c. 


35 


Polj'Duclear, 65 per cent ; lym- 
phocytes, 32; eosinopliiles, 3. 


2 


48 


M. 


4,228,000 


5,000 

6,200 
7,300 


70 


Januar}^ 23d. Stomach and 

Hver. 
January 28th, mealtime. 
January 28th, three hours later. 


S 


66 


M. 




7,000 


70 


February 14th, no cachexia. 








5; 168, 030 


14,400 
19,600 
21,640 


62 


March 6th, Hver involved. 

March 12tli. 

March 17tl), cachectic. 


4 


56 







8,000 
8,500 a.c. 
7.600 p.c. 


85 


Operated. 


5 


45 


.. 


3,536,000 


8,100 


60 




6 


23 




3,120,000 


9,000 
19,000 


20 


Operation. 

Two weeks later. Died. 


7 


37 







9,600 


80 


-f- Omentum. 


8 


41 




4,273,000 


10,000 


57 


Stomach, liver, and glands. 


9 


38 


M. 


5,432,000 


10,190 
13,653 


52 


Januarv 6th. Stomach and 

Hver.' 
January 12th. 
Januarv 22d. Died. 


10 


47 




4,424,000 


11,200 


50 


+ GaU bladder. 


11 


48 






12,800 


45 


-j- Liver. 


12 


41 


. . 




14,000 
14,800 a.c. 
15,600 p.c. 


75 


+ Liver. February 25th. 
February 27th. 


13 


60 







15,000 


60 


+ Liver. 


14 


36 


•• 





15,600 
14,300 


85 


-f- Liver. 


15 


Adult 


M. 


3,352,000 


16,000 




Stomach, liver, and spleen. 


16 


44 




4,128,000 


17,100 


40 


+ Liver. 


17 


29 




5,104,000 


21,000 


72 


-[- Omentum. 


18 


54 


M. 


4,160,000 


24,000 
24,200 
22,500 


60 


Stomach and liver. 


19 


47 


M. 




34,350 

30,600 
105,600! 




November 7th, cancer of stom- 
ach and liver. 

November 11th. 

November 14th, Perforation 
peritonitis. 



CANCER OF THE GULLET. 439 

The variations in the following case are of interest : 
Table XCVII. — Cancer op Stomach with many Metastases. 







. 


■3 


a 
11 


CD'S 


^ 1 


1^ p £v 




d 


1 
3 








rrt 




^ br 








4i C 


g 


o 








t 


S 


? C 


feS 


^Sfe 


n^^'^, 


t- O 


R 


5 


Remarks. 


< 




^ 


^ 
^ 


« 


"I 




>> 


if 

CD 


X3 


t- 
H 




48 


Dec. 20th. 
Dec. 30th. 
Jan. Sd. 
Jan. eth. 


4,816,000 
4,832,666 


13,600 
5,8(30 
8,000 
5,600 


75 
65 

55 


62.0 


23.0 


13.0 


2.0 


Much 


None 


No variation in size. 




Jan. 8th. 








64.0 


26.0 


8.0 


2.0 


Some 


None 


No variation in size. 




Jan. 9th. 


5,224,000 


7,200 


60 


















Jan. 30th. 






55 


















Feb. 2d. 


5,360,000 






















Feb. 10th. 


4,096,000 


6,200 


45 


76.0 


15.0 


8.5 


.5 


Some 




Little variation in size 
and shape. Little poly- 
chromatophilia. 




Feb. 14th. 




15,200 




















Feb. 28th. 


2,496,000 


9,300 


35 


78.5 


20.0 


1.0 


.5 


Some 





No great variation in 
size or shape. No poly- 
chromatophilia. 




Mar. 18th. 


1,944,000 


3,600 


20 


67.3 


23.7 


8.5 


.5 


Some 


None 






Mar. 28th. 


1,784,000 


4,800 


10 


76.0 


16.5 


3.5 


2.0 


Some 


None 


Myelocytes two percent. 
Some poikilocytosis. 
Microcytes. Autopsy. 




April 8th. 


1,152,000 


3,200 


H 

















CANCER OF THE GULLET. 

Most authors are agreed that no increase — in fact usually a de- 
crease — of white cells is the rule m this disease. Thus Eieder 
found 6,900 in one case; Osterspey's two cases showed no leucocy- 
tosis, and Escherich and Pee found similar results.^ This is proba- 
bly due to the fact that the position of the tumor, by causing star- 
vation, tends to lower the leucocytes, while it belongs to a class of 
small, slow-growing cancers which do not as a rule tend to produce 
leucocytosis. 

Nevertheless, 12 of the 26 cases in the Massachusetts General 
Hospital series (see Table XCVIII.) did have leucocytosis, perhaps 
owing to some metastasis or complication. 

Table XCVIII. — Cancer of the Gullet. 













Per cent 








A^e. 


Sex. 


Red cells. 


White cells. 


hasmo- 




Remarks. 


^ 










globin. 






1 


33 






5,400 








a 


68 






5,800 


60 






8 


59 






6,000 


70 






4 


50 






6,400 








5 


58 


M. 


3,488,000 


6,800 


100 


May 11th. 





^ Reinbach's two cases showed a diminution in the polymorphonuclear cells, 
which in all probability means a normal or diminished leucocyte count. 



440 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XCVIIL— Cancer of the Gullet {Continued). 





Age. 


Sex, 


2: 






6 


54 




7 


46 


F. 


8 


62 


.. 


9 


67 




10 


60 




11 


51 


M. 


12 


58 
63 


•• 


13 


56 


M. 


14 


65 


M. 


15 


51 




16 


65 




17 


36 


M. 


18 


49 




19 


64 


•• 


20 


47 




21 


47 


M. 


22 


38 


M. 


23 


67 M. I 


24 


64 




25 


38 




26 


47 





Red cells. 



White P^r ^ent 
cells. haemo- 

globin. 



Remarks. 



4,044,000 



2,824,000 



4,920,000 



6,624,000 



4,604,000 
4,'56(),000 



6.800 

6,800 

7,000 

10,600 

5.400 

6.600 

9,860 

7,000 

13,750 

14,400 

7,000 a.c. 

6,900 p. c. 

7,500 

7,600 

11,500 

7.700 

8,200 

8,725 

11,100 

10,300 

11,800 

11,800 

11,900 

13,000 

14,000 

13,700 

15,400 

15,600 

16.400 

16,400 

20,600 

38,000 

82,000 



60 



60 
50 

75 
90 
72 

68 



30 
90 

80 

70 
80 
60 
60 
65 

80 



May 18th. 

October 18tb. 

October 19th, before food. 
October 19th, after food. 
October 20th. 
December 29th. 
January 31st. 
February 25th. 



Before food. 
Four hours later. 



Hsematuria also. 
Vomitiug. 
January 14th. 
Januarv 21st. 



During digestion. 



January 20th. 

January 30th. Autopsy. 



CAXCER OF THE LIVER. 

(See Table XCIX.) 

Wlajew' records a case in which the red cells fell to 850,000 
with 1.020 specific gravity. 

Of our 53 cases, leucoc^'tosis was present in 29 — over one-half, 
others showing a leucocytosis later — a larger proportion than in 
gastric cancer. The cases were not all primary in the liver or bile 
ducts, but none originated in the stomach, and in all the greater 
part of the growth was in the liver itself. 

The comparatively great diminution in the red corpuscles will 
' Wlajew: St. Petersburg, med. Woch.. 1894, Xo. 43. 



CANCER OF THE LIVER. 



441 



be noted in the Table XCIX. The condition both of red and white 
cells is doubtless due to the rapid growth of tumors of the liver as 
compared, e.g.^ with those of the stomach or lip (see below). 

Table XCIX. — Cakcek of the Liver. 













lie 




6 


Age. 


« 
S 


Red cells. 


White cells. 




Remarks. 


1 


35 




1,680,000 
2,128,000 
1,840,000 


4,800 


20 
20 
20 


August 3d. • 
August 7th. 
August 12th. 








2,968,000 


10,266 


30 


August 19th. 








2,612,000 


8,100 


30 


August 26th. 


2 


55 


M. 


4,170,000 


5,000 




Bile ducts = starting-point. Au- 
topsy. 


3 


61 


M. 


3,824,000 


5,200 


52 




4 


43 







6,200 




Autopsy. 


5 


52 




5,100,000 


6,800 


86 


Bile ducts. 


6 


59 






7,400 






IT 


58 






7,600 


90 




8 


43 




4,060,666 


7,800 


30 




9 


44 


F. 


4,963,000 


7,800 


69 


January 4th, 1896. Autopsy. 








3,784,000 


19,700 


68 


February 12th, 1896. 


10 


59 


M. 


4,570,000 


8,000 




Operated, 


11 


31 


F. 


4,572,000 


8,000 


62 




12 


59 






8,300 


63 




13 


46 






8,500 




Gall bladder. 


14 


48 




4,212,666 


8,700 


56 




15 


72 


M. 


4,100,000 


9,000 






16 


50 


•• 




9,000 a.c. 
10,400 p.c. 


•• 


Bile ducts. 


17 


52 






9,100 
9,100 a.c. 
8,500 p.c. 


75 




18 


54 


M. 


4,072,000 


9,300 




Diff., 1,000 cells: Poly., 82.4 per 
cent.; small lymph., 8.5; large 
lymph., 8.1; old lymph., 1. 


19 


42 




5,600,000 


9,600 


66 


Gall bladder. 


20 


35 


M. 


3,800,000 


12,500 




November 3d \ Poly., 92 per cent. ; 
November 5th v lymph., 8. Au- 










9,800 












22,000 




November 6th ) topsy. 


21 


44 




3,732,000 


9,800 

20,000 a.c. 
18,800 p.c. 


46 


December 5th. Poly., 75 per cent; 
lymph., 22; eosinophiles, 3; reds, 
pale centres. 

December 21st. 


22 




M. 


4,108,000 


9,970 
11,200 


45 


January 1st, 1896. 

January 3d, 1896. Autopsy. 


23 


67 




4,176,000 


10,200 


55 




24 


65 


M. 




10,300 


58 




25 


57 


■ 


3,856,666 


10,400 

11,400 a.c. 
16,600 p.c. 


30 


Poly., 68 per cent.; lymph., 30; 
eosinophiles, 2. 


26 


40 







10,400 


60 


Operated. 


27 


50 


M. 


3,200,666 


10,800 




Primary in bile ducts. Autopsy. 



442 SPECIAL PATHOLOGY OF THE BLOOD. 

Table XCIX.— Cancer op the Liver {Continued). 













C i - 




z 


Age. 


>< 


Red cells. 


White cells. 


III 


Real arks. 


28 


49 






10,800 


80 




29 


53 


•' 


4,456,o66 
4,032,000 


11,000 


65 

68 


April 3d. 
April 21st. 


30 


64 







■iV,266" 

12,650 a. c. 
14,750 pc. 




April 20th. Bile ducts and gall 

stones. 
April 26th. 


31 


57 


M. 




11,150 


50 




32 


69 






11,800 


50 




33 


47 






12,200 


65 




34 


70 







13,000 
28,400 




January 20th. Jaundiced. 
Januarj' 28th. Died January 30th. 


35 


33 







13,600 






36 


48 







14.000 


60 




37 


43 


M. 


4.160".066 


14,100 




July 17th. Autopsy, July 19th. 


38 


56 




3,956,000 
5,120,000 


14,200 

14,900 a. c. 
17,800 p.c. 


47 
65 


Poly., 84 per cent; lymph., 15.6; 

eosinophiles 4. 
January 17th. Gall stones. 

January 24th. 


39 


52 






'15,566* 


70 




40 


52 




4.400,666 


15,600 


75 






64 


M 


2,768,000 

2,880,000 

2,928,000 


15,800 

21.900 

1,530 

11,700 


45 
45 


May 6th. 
May 24th. 
May 28th. 
June 8th. 


41 


31 






15,700 
13,100 


80 


February 27th. 
February 28th. 


42 


30 


F. 


3,660,000 


17,200 
16,800 
17,500 


82 


Poly., 83 per cent; myelocyte. 1. 


43 


48 




2,900,000 


48 


Poly., 92 per cent; lymph. 5.8; 














eosiuophile, 1 ; myelocytes. 2. 














Autopsy. 


44 


63 




3,864,000 


17,600 


55 




45 


31 


M. 


3,130,000 


18,700 
15,600 
14.000 


52 


December 20th. 

December 30th. Before food. 

December 30th. Four hours later. 


46 


37 




• 


20,600 
19.000 a.c. 
20,000 p.c. 






47 


66 




3,704,000 


21,000 


50 




48 


58 






23,200 
22.200 




January 31st. 

February 12tli. Abscess of liver. 


49 


45 


•• 




24,400 
17,200 


70 


March 14th 


50 


Adult 


M. 


4,408,000 


25,500 


70 




51 


65 


* * 




27,000 
17,000 
13,000 


70 


April 12th. 
April 14th. 
April 16th. Diff. count 500 cells: 












Poly., 85.6 percent: small ivmph., 














11.6; large lymph., 2.8. 



CANCER OF THE INTESTINE. 
Table XCIX. — Cancer of the Liver {Continued). 



443 



c 


Age. 


1 


Red cells. 


White cells. 


III 


Remarks. 


52 


46 




2,824,000 


32,600 


33 


Omental hernia. Purpura haemor- 
rhagica. Internal hemorrhage. 
Poly., 84.8 per cent; lymph. 15.2; 
eosinophiles, 0; no nucleated reds; 
considerable variation in size ; mod- 
erate poikilocytosis. 


53 


50 


M. 


4,544,000 

3,136,000 
4,056,000 


35,600 
36,400 
23,000 
28,000 


•• 


November 29th. 1895. 
December 10th, 1895. 
January 15th, 1896. 
February 16th, 1896. Autopsy. 



Jan. Feb. 



28,000 
26,000 
24,000 
20,000 
18, 000 
16,000 
14, 000 
12,000 
10,000 



24 




28 


30 


4 


5 


8 


9 


10 


11 


12 


13 


14 


















A 
























y 


k^ 


\ 










/ 












/ 


/ 






1 




A 


■ 


/ 






















/ 




V 
























/ 


















^ 








/ 




























V 












/ 


/ 


\ 


4 














Di 


edo 


nl5 


th 































Fig. 31. —Chart of Leucocytes in a Case of Cancer of the Liver. 



CANCER OF THE INTESTINE. 

The leucocyte counts range both high and low, 

Hayem ^ found cancer of the rectum to show only 9,500 leuco- 
cytes. Reinbach '^ found in three cases of cancer of the rectum mod- 
erate leucocytosis.^ Only 15 of the 39 cases in our series (see Table 
C.) showed leucocytosis, and in one of these there was a compli- 
cating pylephlebitis which probably raised the count. 

The red cells show little change. 



' Loc. cit. 
^ Apparently- 



- Loc cit. 
■that is, the percentage of polynuclear cells was increased. 
He did not count the leucocytes as a whole. 



444 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table C. — Cancer of the Intestine. 





Age. 
28 


Sex. 
M. 


Red cells. 


White 
cells. 


Perct. 

haenio- 

j globin. 


Remarks. 


1 




' 5,300 


1 72 


Cancer of ca?cum. Operation. 


2 


59 


F. 


4,800,000 


5,500 


1 33 


Cancer of ctecuni. Autops3^ 


3 


33 


M. 


4,368,000 


5.800 


83 


Cancer of colon. Operated. 


4 


41 


F. 


5,560,000 


5,800 


45 


Cancer of cjx^ciim operated suc- 
cessfully. 


5 


59 




.... 


6,000 


33 


Decern ))er 7 til. 








3,452Vo()b 


i 


40 


December 9th Polynuclear. 65.6 
per cent : lymphocytes, 31.4; 
eosinopliiles, 3. 








3,840,000 


! 11,700 


40 


December 21st. 


6 


62 






, 6,400 a.c. 
' 10,000 p. c. 


•• 


Hepatic flexure. 


7 


28 






' 6,600 


84 


Hepatic flexure. 


8 


66 


M. 


4*268,000 


7,150 


78 


Cancer of intestine (where?). 


9 


38 






7,200 


85 


Sigmoid 


10 


23 






7,200 


90 


Rectum. 


11 


59 






7,400 


70 


Splenic fle.xure. 


13 


52 


M. 




7,400 


55 


Metastases, primary in sigmoid. 


13 






3,'504,00'0 


7,400 a.c. 
8,300 p. c. 


50 


Hepatic flexure. Polynuclear. 80 
per cent: lymphocytes. 19; 
eosino])hilc, 1. 


14 


39 







7.500 






15 


52 


M. 


2,424, boo 
2,440,000 


7,800 
6,800 




Cancer of caecum. No digestion 
leucoc3'tosis. 


16 


50 






7,800 






17 


50 






8,600 


90 


Rectum. 


18 


31 


M. 


i.oiiVooo 


8,800 




Cancer of hepatic flexure. Op- 
erated. 


19 


32 


• • 




9.000 


75 


Sigmoid. 


20 


47 


F. 




9,300 


63 


Cancer of cnecum. 


21 


36 




3.004.000 


9,800 


40 


Operated. 


22 


62 




4,416,000 


10,000 


65 


Hepatic flexure. 


23 


53 




4,992,000 


10,000 


51 


Descending colon. 


24 


34 




4,524,000 


10,800 


38 


Rectal. "Polynuclear, 78 per 
cent; lymphocytes, 19.8; eo- 
sinophiles, 2.2. 


25 


45 




3,358,000 


11,500 


25 


Polynuclear, 68 per cent; lym- 
phocytes, 28.5; eosiuophiles, 
3.5. 

Cancer of Rectum. 


26 


50 


F. 


5,416,000 


12,000 




27 


49 




4,872.000 


12.300 


50 


Rectum with metastases in liver. 


28 


56 


ir. 


4,408,000 


12,700 


60 


Cancer of duodenal papilla with 
pylephlebitis. Autopsy. 


29 


17 






13,600 






30 


53 




5,960,000 


13,700 


60 




31 


58 






15,000 


85 


Transverse colon. 


32 


58 


M. 


4,*16b,00b 


15,200 


50 


Cancer of rectum. Operation. 


33 


45 






15,400 


70 


Rectum. 


34 


34 


M. 




15.500 


40 


Metastases, primary in sigmoid. 


35 


46 







21,600 


80 


Rectal and omental. 


36 


58 






24,000 


85 


Cancer of sigmoid. 


37 


62 






25,200 


75 




38 


20 







26,700 


98 




39 






2,760.000 




15 


Cancer of caecum. Julv 16th. 








2,480.000 




15 


.July 19th. 



CANCER OF OMENTUM AND ABDOMINAL ORGANS. 445 



CANCER OF OMENTUM AND ABDOMINAL ORGANS 
GENERALLY. 

The twenty-three cases seen at the Massachusetts General Hos- 
pital in which cancerous tissue was pretty generally distributed 
through the abdominal organs, all showed leucocytosis with eight 
exceptions (see Table CI.) 

Table CI. — Cancer of Omentum and Abdominal Organs Generally. 













Per cent 




• 


Age. 


>i 


Red cells. 


White cells. 


haemo- 


Remarks. 


z 




^ 






globin. 




1 


50 


F. 




Greatly 
increased. 


Markedly 
dimin- 
islied. 


Primary in pancreas. Difl. 
count of 400 cells ; Poly. , 84. 5 
per cent; small lymph., 8; 
large lymph., 5; eosinophiles, 
2.5. Autopsy. 


2 


63 




5,440,000 


5,350 




Colon. 


3 


47 




6,072,000 


5,800 


65 




4 


59 




3,452", 666 


6,000 


35 

40 


December 9th. Poly., 65.6 per 
cent ; lymph., 31 ; eosinophiles, 
3 ; basophiles, 4. 








3,840,000 


11,700 


40 


December 21st. 


5 


64 


. . 


3,512,000 


7,000 


62 


Bladder. 


6 


48 


M. 




7,250 
6,500 [ 
7,300 [ 


• • 


May 13th. 

May 20th. No digestion leuco- 










cytosis. 


7 


42 


M. 


4,560,000 


7,800 
10,600 


60 


October 13th. Poly., 88 per ct. ; 

lymph., 10; eosinophiles, 2. 
October 16th. 


8 


67 






7,800 a.c. 
8,100p.c. 






9 


47 






8,000 
8,300 


65 


Caecum. 

General in abdomen. 


10 


70 






8,700 


60 


Gall bladder. 


11 


26 


M. 





9,000 






12 


63 




2,860",660 


10,600 
9,600 


35 


Poly., 84 per cent; lymph., 
10.2; eosinophiles, 6; myelo- 
cytes, 8; normoblasts, 1. 


13 


40 


M. 


2,208,000 
1,875,000 


11,500 
15,600 


55 


December 13th. Peritoneum. 

December 19th. 

December 13th. Diff. count 

400 cells: Poly., 83 per cent ; 

lymph., 16; eosinophiles, 1. 
December 19th. Polynuclear, 

80 per cent ; lymphocytes, 20 , 

eosmophiles, 0. 


14 


65 


M. 




11,700 






15 


44 






13,600 
14,200 


68 


February 10th. 

February 18th. PeritoneaL 
Autopsy. 



446 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table CI.— Cancer of Omentum and Abdominal Organs Generally 

{^Continued). 











White 


Per cent 




^ 


Age. 


X 


Red cells. 


cells. 


haemo- 


Remarks. 


2 




^ 






globin. 




16 


Adult 


M. 


3,772,000 


13,700 




Autopsy. 


17 


62 




3,840,000 


14,400 

7,800 


60 
70 


November 14th. Abdominal. 
November 23d. Secondar}- in 

liver and glands. 
November 14th. DiflF. count 

400 cells: Pol}'., 77 per cent; 

lymph., 22; eosinophiles, 1. 
November 23d. Poly nuclear, 

69.5 per cent; lymphocytes, 

30; eosinophiles, 0.5. 


18 


28 




4,496,000 


152,000 


45 


Peritoneal. 








2,995,000 


18,000 


60 


Poly., 79 per cent; lymph., 
14.5; eosinophiles, 3.5. Kidney 
and spleen. 


19 


46 




8,000,000 


20,400 
12,600 


50 
65 


Poly.. 88 per cent; lymph., 10; 
eosinophiles, 2; Normoblasts. 
16: megaloblasts, 2. Count 
500 cells. Size of reds normal. 


20 


60 






25,000 


62 




21 


Adult 


F. 


5,500,666 


26,200 




Autopsy. 


22 


45 


F. 




27,400 




Questions of aneurism. Au- 
topsy. 
Ditf. count of 500 cells; Poly., 


23 


Adult 


M. 




Greatly 


Markedly 










increased. 


dimin 
ished. 


80 percent; lymph., 20. 



CANCER OF THE KIDNEY. 

Of ten cases which I have examiued (see Table CII.) eight 
showed large leucocyte counts— viz., 12,900, 19,980, 25,000, 27,000, 
28,500, 43,100, 82,000, and 91,000. In three of these cases, how- 
ever, the tumors maj^ have been sarcomata, as no microscopical ex- 
amination was made. Most of the cases had fever, chills, and signs 
of inflammation, which may account for part of the leucocytosis. 



Table CII.— Cancer (or Sarcoma) of Kidney. 



1 


< 

68 
48 
76 


(-5 


Red cells. 


White cells. 


Per cent 
hsemo- 
globin. 


Remarks. 


1 

2 
3 


•• 


3,840,000 

5,'d46,bbb 


7.600 
8,100 
9,100 


50 
45 


Autopsy. 
Sarcoma. 



CANCER OF THE UTERUS. 447 

Table CII. — Cancer (ok Sarcoma) of Kidney {Continued). 



10 



< 


1 


Red cells. 


14 






53 


M. 


.4,312,000 


2 


F, 


3,756,000 


57 


F. 


5,200,000 


49 


F. 


3,360,000 


50 


F. 


4,111,000 

2,780,000 



White cells. 



19,980 
11,600 a.c. 
12,900 p.c. 

7,900 a.c. 

9,000 p.c. 
23,000 
25,090 



27,000 



28,500 



43,100 



82,000 
91,000 



Per cent 
hsemo- 
prlobin. 



32 



Remarks. 



Autopsy. 

March 14th. Polynuclear, 72 per cent.; lympho- 
cytes, 27 ; eosinophlle, 1. 
March 17th. 

Autopsy. 

Differential count of 800 cells : Polynuclear, 80,9 
percent.; lymphocytes, 15.8 ; eosinophiles, 3.3. 
No nucleated red cells. 

Differential count of 500 cells : Polynuclear, 66- 
per cent.; lymphocytes, 29.5; eosinophiles, 2; 
myelocytes, 2.5 ; normoblasts, 24 ; megaloblasts, 
2. Autopsy. 

Supposed leukaemia. Differential count of 500 
cells: Polynuclear, 81.8 percent.; small lym- 
phocytes, 12; large lymphocytes, 4.2; eosino- 
philes, 2. Autopsy. 

Supposed leukaemia. Differential count of 1,000 
cells: Polynuclear, 92.9 per cent.; lymphocytes,^ 
6.2; myelocytes, .9; normoblasts, 2; megalo- 
blast, 1. Autopsy. 

July 8th. 

Polynuclear, 98 per cent.; lymphocytes, 2. 



Von Limbeck's ' case mounted steadily from 18,514 to 80,541. 

CANCER OF THE UTERUS. 

In six cases Hayem ^ found no increase — the counts ranging from 
4,575 to 9,500, with an average of 7,800. 

Rieder,^ on the other hand, in a single case found 30,800, and 
the seven cases counted at the Massachusetts General Hospital 
showed a leucocytosis in five (see Table CIII.). 

There is need of more data on this subject. 

Table CIII. — Cancer op the Uterus. 



Age. 


X 




m 


35 




45 




42 




43 




43 




59 





Red cells. 



3,716,000 



4,773,000 





Per cent 


White cells. 


haemo- 




globin. 


6,400 


62 


8,200 


75 


8,200 


35 


8,600 


43 


11,900 


70 


16,800 




7,400 a.c. 




12,000 p.c. 





Remarks. 



Dife. count 500 cells: Poly., 68 
per cent; small lymph., 23; 
large lymph., 8; eosinophiles, 1. 



First day. 
Third day. 



^ Loc. cit. 



'^ Loc. cit. 



Loc. cit. 



448 SPECIAL PATHOLOGY OF THE BLOOD. 

Table CIIL — Cancer oe the Utekus {Continued). 











White 


Per cent 






Age. 


5 


Red cells. 


cells. 


haemo- 


Remarks. 


"^ 




CO 






globin. 




7 


48 


F. 


2,696.030 
3,232,000 


19,400 
30,700 


20 


October 26th. 
October 28th. 


8 


51 


F. 


• 


34,900 


■ 


Diff. count of 1,000 cells: Poly., 88 
per cent; small lymph., 11.7; 
eosinophiles, 0.2; myelocytes, 
0.1. Two normoblasts. 


9 


31 


F. 


2,889,680 


22,250 






10 


28 


F. 




20,170 


75 


Ureter blocked : anuria nine days. 
Autopsy. 


Table CIV.- 


-Cancer of the Ovary. 










White 


Per cent 




o 


Ape. 


Sex. 


Red cells. 


cells 


haemo- 


Remarks. 


2 










globin. 




1 


50 




3,o32,00C 


16,400 


50 




2 


36 


F. 


4,500,000 


25,000 


62 


Operation. 


3 




F. 


3,248.000 


32,800 




Operation. 


Cancer 


OF THE Prostate. 


1 


63 




2,596.000 
2,212.000 


9,200 
11,000 


35 


December 13th. 
December 19th. 

Polynuclear, 74.4 per cent; lym- 
phocytes, 23.6; eosinophiles, 2. 


2 


45 


M. 





10,200 






3 


51 






18,000 







1 1 51 I M. 



1 


60 




2 


46 




3 


57 




4 


? 


F. 


5 


41 




6 


67 




7 


4 




8 


44 




9 


y 


F. 


10 


31 


F. 


11 


54 


■ ■ 


12 


71 


.. 


13 


63 




14 


32 


.. 



Cancer of the Lip. 
7,000,000 1 6,300 I I 

Cancer of the Breast. 

First day. 
Third day. 



5,200,000 



18,000 




14,000 




15,200 


100 


12,200 


68 


Marked 




11,900 


70 


11,000 


85 


9,300 


90 


8,500 


80 


Not in- 




creased. 




8,200 




8,200 


65 


12,800 




8,000 


80 


10,500 




7,600 


85 


7,200 


85 



Diff. count 400 cells: Poly., 89 per 
cent; lymphocytes, 11 percent. 

Recurrent. 

Both breasts. 

Diff. count of 600 cells; Poly., 72.4 

per cent; lymphocytes, 25.4; 

eosinopbiles, 2.2. 

June 16th. 
July 4th. Death. 
January 16th. 
January 25th. 



CANCER OF THE UTERUS. 

Ca^ceh of the Xeck. 



449 



c 
Z 


Age. 
42 


Sex. 
M. 


Red cells. 


White 
cells. 


Per cent 
baemo- 
crlobln. 


Remarks. 


1 

2 




Marked 

increase. 

20,000 




Poly nuclear, 88.5 per cent. 



27 



35 



Metastatic Glandular Cancer. 



38,700 
6,900 



February 15th. 

February 21st. Autopsy. 

Diff. count, 400 cells: 

February 16th. Poly., 54.4; lym- 
phocytes, 42.7; eosinophiles, 2.9. 

February 17th. Poly., 66.2; lym- 
phocytes, 30; eosinophiles, 1.8. 



Cancer in Ethmoidal Cells. 



55 


M. 


56 


M. 


64 


M. 


56 




52 




49 




50 





I 62 I F. I 



I 59 1 M. 



27,800 




July 11th. Diff. count, 400 cells 
Poly., 83.5 per cent; lympho 
cf^^tes, 15.8 per cent; eosino 
philes, 0.7 per cent. 


21,500 




July 23d. 


22,100 




July 27th. 


17,000 




July 30th. 


24,000 




August 1st. 


29,700 




August 5th. 


20,400 




August 9th. 


21,400 




August 12th. 


22,600 


• 


August 16th. 


Cancer of 


the 


Pancreas. 


18,300 7 





Metastases. 


17,600 




Liver and spleen also. 


15.900 




General peritonitis. 


11,000 7 


5 


Head. 


10,500 6 


5 


December 28th. 


14,600 




January 1st. 


22,000 






10,000 8 





January 3d. 


6,100 7 


■y 


June 17th. 


7,222 i . 




June 22d. 


Cancer oi 


-^ Ye 


rtebr^. 


13,200 1 







Adenoma of the Suprarenal Body. 

, . . I 24,200 I . . I Autopsy. 



Mediastinum. 



1 25 



5,008,000 



29 



10,700 
9,300 
8,300 
6, MOO 

12,800 

14,000 



70 



30 



April 20th fPolynuclear, 87 per 
April 26th J cent; lymphocytes, 
April 27th ] 12 per cent ; eosino- 
May 1st [ philes, 1 per cent. 
July 7th. Stricture of oesophagus. 

Larynx. 
July i8th. Xo autopsy. 



450 SPECIAL PATHOLOGY OF THE BLOOD. 

Skull. 





ARe. 


Sex. 


Red cells. 


z 








1 


57 






2 


70 


' ' 


■*•■*•'' 



White 
cells. 



1 Per cent 
I haemo- 
I globin. 



Remarks. 



63 



4,700,000| 



9,200 

8,600 

15,800 

14,600 



14,600 
5,000 



; Cerebral. 
! May 7th. 

May 22d. 

May 28tli. 



Metastases. 



General. 

70 j 
60 



Multiple myeloma. 
Cancer of the Bladder. 



(Wright.) 



55 




2,856,000 


12,600 


42 



Papilloma. Diff. comit, 500 cells: 
Polynuclear, 63.4 per cent; small 
lymphocytes, 29 per cent; large 
lymphocytes, 6 per cent ; eosino- 
philes, 1.6 per cent. 



I 63 



C.\NCER OF Pleura. 
20,000 ' 65 I Endothelioma. 



Autopsy. 



Cancer of the Iq^ has apparently been neglected so far as blood 
examination is concerned. Hayem, Rieder, and Eeinbach give but 
one case each, the counts being respectively 7,000, 11,600, and 
"not increased." In a single case at the Massachusetts General 
Hospital I found 6,300. 

The following scattered counts may be added : Cancer of tongue, 
7,000 (Hayem); cancer of scrotum, 6,700 (Hayem); cancer of 
navel, 7,100 (Hayem); cancer of larynx, 7,200 (Hayem), 16,000 
(Reinbach); cancer of pancreas : Hayem, 2 cases — 9,400 and 9.900; 
Schneider, 1 case — 12,000; cancer of vagina, 9,800 (Rieder); can- 
cer of penis, 7,000 (Hayem); cancer of thyroid, 70,000 (Hayem) 
a very rapidly growing tumor; cancer of mediastinum, "marked in- 
crease" (Reinbach); cancer of prostate,' 10,200. 

Qualitative Changes in the Leucocytes. 

1. The percentage of polymorphonuclear neutrophiles is usually 
high in cases with leucocytosis and normal in those without it. 

^ Braun (Wien. med. Woch., 1896, p. 582) mentions a cancer of the pros- 
tate in which the leucocj^tosis, instead of being made up mostly of polynuclear 
leucocytes, was associated with a large increase of the small lymphocytes 
together with numerous eosinophilic myelocytes. 



CANCER OF THE UTERUS. 451 

This rule holds for perhaps three-fourths of the cases ; but there 
are many exceptions to it. For instance, Taylor^ reports 27,840 
leucocytes with 60.6 per cent polymorphonuclear cells, 14,800 leu- 
cocytes with 66.2 per cent polymorphonuclear cells, 25,000 leuco- 
cytes with 58.2 per cent polymorphonuclear cells, 45,000 leucocytes 
with 43.7 per cent polymorphonuclear cells, the last a marked lym- 
phocytosis. On the other hand, he found 88,7 per cent of poly- 
morphonuclear cells in a total leucocyte count of 3,000. My own 
experience and Cunliffe's is similar — i.e., 88 per cent of polymorpho- 
nuclear cells with a total count of 7,800 leucocytes, though I have 
never seen so marked a lymphocytosis as was present in Taylor's 
cases. He also noted a relative increase in the large lymphocytes 
which my counts and those of Canliffe have not shown. Osier and 
McCrae found an average of 81 per cent of polymorphonuclear cells 
in 22 cases, the higher percentages being in the cases with highest 
total leucocyte count. These writers confirm the observation of 
Taylor that the large mononuclear and transitional leucocytes are 
often relatively increased in cancerous disease. Taylor found in 15 
cases with leucocytosis an average of 19.3 per cent of these cells 
and in 6 cases without leucocytosis 26 per cent. Eight of these 
cases were cancer of the stomach — the remainder cancer of other 
organs. All were cachectic. Osier and McCrae in 22 cases of gas- 
tric cancer record an average of 8.5 per cent of large mononuclear 
and transitional varieties. They do not agree with Taylor in be- 
lieving the excess of these cells is sufficient to be of diagnostic value. 
Keinbach found in 8 cases with leucocytosis 89 per cent in 2 
cases and 87, 86, 83, 81, 80, and 77 per cent in others. Cunliife 
{loG. cit.) in 86 cases found an average of 73.4 per cent polynu- 
clear. There was marked lymphocytosis in 3 cases. In the Massa- 
chusetts General Hospital series the following percentages occurred : 
When no leucocytosis was present, 88.7, 88, 86, 79, Q)Q, 62.5, 62, 
60, 57 per cent, etc. With leucocytosis, 96, 98, 92, 90, 90, 88, 
87, 86, 84, 83, 74 per cent, etc. (see Tables XCVI., XCIX., CI., 

cm.). 

2. Eosinojphiles are not always notably decreased (as they are in 
many other leucocytoses), nor are they regularly increased. In 
Reinbach's 16 cases the average percentage was 2 -j- per cent. In 
Osier's 22 cases it was 1.1 per cent. In Cunliffe's 86 cases 1.06 
per cent, although 6 cases showed eosinophiles, and the highest (9.8 
1 Taylor: Internat. Med. Mag., July, 1897. 



452 



SPECIAL PATHOLOGY OF THE BLOOD. 



per cent) in cancer uteri In the Massachusetts General Hospital 
cases the average was 1.2 per cent, but in 7 of the 38 cases in which 
differential counts were made no eosinophiles were seen. Chri>- 
tian (Jv//. Med., January 24th, 1902) reports a case of enormous 
cancerous growth in the liver (thirty-three pounds weight). T\\v 
following counts were recorded nine months before death, and show 
w a viced eosln ojth din . 



November 8th, 1900. 



l^ed cells 3,704,000 

White cells 8,600 

Haemoglobin 75 per cent. 

Fol\ nuclear 40.5 per cent. 

Lymphocytes 31.5 

J^arge lymphocytes .. . 9.5 

JEosinophiles 1:15 ! 



November ti4th, 19(»ti. 



Red cells 3,952,000 

White cells 9,800 

Haemoglobin 50 per cent. 



Polynuclear (333) 50.8 per rent. 

Lymphocytes 38.7 

Large lymphocytes . , 38.7 

I Eosinophiles 10.5 



3. Miji'loci/ti's. — Perhaps more commonly tliau in other condi- 
tions except leukaemia and pernicious anaemia, we tind in malignant 
disease small percentages of myelocytes. 

About one-half of all the cases of cancer examined b}- me have 
shown m3-elocytes. Cimlifte noted them m 6 cases out of 8(). 

Epstein ' in a case of cancer with metastatic bone nodules noticed 
large luimbers of nucleated corpuscles (normoblasts and megalo- 
blasts) and myeloc^'tes, but I think the association was a mere coin- 
cidence, since I find that myelocytes and erythroblasts are very com- 
monh^ present in cachexia with auiemia from any cause. 



SARCOMA. 



In general the effects of sarcoma are like those of cancer, but 
worse. The literature of the subject is rather scanty. 

Red Cells, — Ha3'em in a case of osteosarcoma counted the red 
cells at 663,400 per cubic millimetre. 

Laker ^ describes an "abdominal cystosarcoma '" in which two 
cotmts of red cells showed 2,800,000 and 2,500.000. 

Von Limbeck ^ in 1 case found 1,118,000, and in another 2,240.- 
000. Both were osteosarcomata. 



^ Wiener med. Presse, December, 1894. 
^ Wien. med. Woch., 1886. p. 926. 



^ Loc. cit. 



348. 



SARCOMA. 



453 



Sadler^ in 3 cases foiuul 2,710,000, 3,637,000, and 4,500,000. 

E-ieder- in 3 cases (all osteosarconiataj found 1,846,160, 3,700,- 
000, and 3,995,000. 

Da Costa in 14 cases found the red cells ranging from 5,400,000 
to 2,510,000 with an average of 3,900,000. The haemoglobin from 
83 to 42 per cent, averaging 63 per cent, and the white cells from 
7,000 to 40,000, averaging 13,276. Only 3 of his 14 cases had over 
15,000 leucocytes. Cunliffe, in 19 cases affecting various organs, 
found the highest count 5,150,000, the lowest 2,240,000, the aver- 
age 4,260,000. The haemoglobin averaged 62 per cent, color index 
0.73. Normoblasts were seen in 2 cases. The leucocytes ranged 
from 5,400 to 32,000, averaging 14,960. The polynuclears were 
relatively increased in 18 out of 19 cases. Eosinophils increased 
in 2 cases (6 and 9.4 per cent). 

The Massachusetts General Hospital blood counts include 22- 
cases in which the red cells Avere counted (see Tables CV. and 
CYI.), the average being 4,500,000, not nearly so low as that re- 
corded by other observers; still low counts occurred (2,706,000, 
2,637,000, 3,842,000). 

The qualitative changes in the red cells consist (as in cancer) of 
the '"degenerative" changes (deformities in size and shape, englo- 
bular changes) present in marked cases, and the presence of nu- 
cleated corpuscles, when cachexia is marked. 

Tabi-e CV. — Sarcoma with Leucocytosis. 



Age. 


Sex. 


41 


M. 


21 


F. 


20 




mts. 




29 




30 


•• 


32 


ii. 


63 





Red cells. 



4,188,000 
3,842,000 
2,706,000 
4,000,000 



4,512,000 
5,422,000 



4,312,000 
2,630,000 
2,900,000 



White 
cells. 



Per cent 
haemo- 
globin. 



98,000 
71,000 
56,000 
44,600 

36,000 

26,100 
28,500 



25,000 
24,000 
21,000 
22,000 



00 

42" 



32 

50 

'ss' 



Remarks 



L>c. (lit., pp. 38, 39. 



Polynuclear cells, 90.2 per cent. 
Sarcoma of lung, etc. Autopsy. 
Sarcoma of kidne}'. Autops}'." 
Polynuclear cells, 70 per cent. 

Melanotic sarcoma; perforation of 
intestine ; peritonitis. 

Xeck. 

One month later. Polynuclear, 89 
per cent; lymphocytes, 9.8; 
eosinophiles, 1.2. 

Polynuclear, 80.9 per cent. 

General sarcomatosis. 

One week later. Autopsv. 

Chest wall. Polynuclear, 76.5 per 
cent; lympliocj'tes, 23; eosino- 
philes, 0.5. 

Loc. cit., pp. 98, 100. 



454 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table CV.— Sarcoma with Leucocytosis {Continued). 



10 
11 
12 



Age 

8 
58 
45 



60 

adit. 

36 



17 

18 
19 



20 
21 



23 

24 



25 
26 

27 



28 
29 
30 
51 
32 



46 

68 
48 



28 



22 58 



34 



24 



57 



31 
36 
49 
10 
54 



Sex. 



M. 



Red cells. 



White 
cells. 



5,480,000 



4,560,000 



M. 



M. 



4,700,000 
6,200,000 



4,352,000 
4,"l80,00b 

4,712,000 



21,800 
19,980 
18,400 
21,600 
16,600 
18,300 
18.000 
17.200 
17,000 



23.900 
33,400 
37.900 
41.200 
33,000 
36,000 
40,200 
55,400 
16,000 
19,000 
16.000 
Marked 
increase. 



Per cent 
haemo- 
globin. 



15,200 

Great 

increase. 



14,100 

14,000 

Great 

increase. 



13,600 
13,200 
13,000 
16,250 
15,180 
13,000 
11,000 
10,900 
10,200 
9,800 



40 

80 



65 



80 



80 



47 



95 
85 
60 

70 

70 



Remarks. 



Testicles. Autopsy. 

Neck. Autopsy. 

December 2d. Adrenal. 

December 5tli. 

December 16tli. 

Rib. 

Sarcoma of abdominal organs. 

Lung. Autop.sy. 

3Ielauotic .sarcoma of all the ab- 
dominal organs (bone metasta- 
sis?). November 30th, 1895. 
Diflf. count, 600 cells: Poly nu- 
clear. 71 percent; small lympho- 
C3'tes, 11 ; large lymphocytes. 
5.2; eosinophiles, 12.4 (!); mye- 
locytes, 4. 

December 7th. 

December 13th. 

December 19th. 

December 22d. 

December 26th. 

January 14th. 

January 28th. 

Sarcoma of abdominal organs. 

Three days later. Autopsy. 

Sarcomatosis. 

Diff. count, 700 cells : Polynuclear, 
70 per cent: lymphocytes, 22: 
eosinophile, 1 ; myelocytes, 7. 
Sarcomatosis. 

Sarcoma of intestines. 

Osteosarcoma (thigh). Diff. count, 
500 cells: Polynuclear, 74 per 
cent: small h'mphocytes, 19: 
large lymphocytes. 6^ eosino- 
philes, 1. 

Caecum. 

Right pubic bone. 

Sarcoma of abdominal orsraus. 
Diff. count, 800 cells: Polynu- 
clear, 84 percent: lymphocyte?. 
15.5; eosinophiles. 1.2. 

Sarcoma of kidney. 

Sarcoma of abdominal wall. 

Melanotic sarcoma of abdominal 
organs. 

One week later 

Adrenal. 

Uterus. 

Left kidney. 

Abdominal wall. 

Kidney operated. 



SARCOMA. 



455 



Small tumors are often without any effect on the blood (see 
Table CVI.). According to v. Limbeck^ this is oftener true than 
in cancer. 

Table CVI. — Sarcoma without Leucocytosis. 











White 


Pei^ cent 






Age. 


Sex. 


Red cells. 


cells. 


haemo- 


Remarks. 


:S 










globin. 




1 


38 







9,500 


80 


Sarcoma mediastinum; metastasis 
of spine. Autopsy. 


2 


37 


J^\ 


4,980,000 


9,000 


78 


Sarcoma of ovary. 


3 


? 


M. 


4,946,000 


9,000 




Osteosarcoma of shoulder. 


4 


40 






9,000 


75 


Liver, secondary. 


5 


29 


M. 


5,280,000 


8,200 


.... 


Sarcoma of testicle. 


6 


26 




4,800,000 


8,000 


30 


Sarcoma of lung. Autopsy. 


7 


44 




....,.., 


7,600 


70 


Ovary. 


8 


41 







7,400 


80 


Metastatic liver, secondary. 


9 


36 


M. 




6,700 






10 


58 






6,500 


.... 


Cutaneous. 


11 


46 




5,390,000 


6,100 


55 


Glands. 


12 


24 


M. 


4,952,000 


6,000 




Small recurrent sarcoma of groin. 


13 


70 




4,520,000 


6,000 


70 


Multiple small round cell. 


14 


34 






6,000 


78 


Recurrent. 


15 


47 




4,288,000 


5,600 


65 


Kidney operated. 


16 


35 






5,100 
5,700 a.c. 
8,600 p.c. 


65 


Retroperitoneal. Polynuclear, 66 
per cent; lymphocytes, 33.4; 
eosinophiles, 0.6. Reds good. 



Hcemoglohin. — Reinbach's^ 20 cases ranged between 23 and 75 
per cent, averaging 52 per cent. 

Bierfreud ^ in 29 cases found variations between 40 and 75 per 
cent. 

Von Limbeck's 2 cases had 28 and 48 per cent respectively. 

Rieder's' 4 cases showed at the beginning of treatment 29, 56, 
57, and 65 per cent respectively, but in 1 case the haemoglobin went 
down gradually while under observation until it reached 6 per 
cent ( !), the lowest point, Eieder says, that he has ever seen in any 
disease. 

Sadler's ' cases showed 33, 45, and 78 per cent. 

In the 16 cases of Table CYI. in which this point was noted, the 
average is 59 per cent. 

On the whole, the coloring matter seems to be more diminished 
than in most cases of cancer. 

Leucocytes. — The following tables, slightly modified from v. 
Limbeck, show the important points : 

1 Log. cit. ^ X()c. dt. ^ Loc. cit. ^ Loc. cit. ^ Loc. cit. 



456 



SPECIAL PATHOLOGY OF THE BLOOD. 



No. 


Observer. 


Diagnosis. 


Count. 


1 


Hayem. 

Alexander. 

(( 

(( 
(( 

u 
u 
u 

Alexander. 

Rieder. 
(( 

(C 

V. Limbeck. 

.4 

Reinbacli. 
Mass. General Hospital. 

u n u 


Osteosarcoma. 

a 

M 

Osteosarcoma. 

(( 

(( 

(( 
(( 
t( 

M 

(( 
M 


11.250 
52,700 
16,430 
16,275 
17,050 
15 90(» 


2 


3 


4 


5 


6 


15,570 
13,020 
10,950 
12,090 
11 '^48 


7 


8 


9 


12 700 


10 

11 

12 

13 


10,900 
9,100 
8,000 
32,000 
26,800 
20,000 
13.000 
21 000 


14 

15 


16 


9.000 










Average, 


17,000 ± 



No. 


Observer. 


Diagnosis, 


Count. 


1 


Hayem. 
Alexander. 

a 
u 

V. Limbeck. 
Sadler. 


Lymphosarcoma. 

(( 
(( 
(( 

(( 

u 
u 

u 
u 


11,700 


2 

S ..... ..... 


19,910 
19 530 


4 


11,696 


5 

6 


11,470 
10,540 


7 


55,100 


8 


38,000 


9 


10,800 


10 


33,248 


11 


19,299 


12 


9,044 






Average, 


20,000 4- 



No. 


Observer. 


Diagnosis. 


Count. 


1 


Rieder. 

Reinbach. 
Mass. General Hospital. 

a u u 


Melanosarcoma, 

(( 
(( 
u 
(( 


41,600 


2 


28 500 


3 


22,. 300 


4 


25,000 


5 


8 000 


6 


37,900 


7 


13,000 










Average, 


25,100 + 



SARCOMA. 
Table CV'IL — Multiple Myeloma. 



457 







White 
cells. 


Per cent 


Per cent 




X 


Red cells. 


haemo- 


poly- 


Reporter. 


'/^ 




globin. 


nuclear. 




1 


5,030,000 


11,600 


35 


74 


Fitz: Am. Journ. Med. Sc, vol. 
ex vi., .1898. 


o 


3,200,000 


16,000 


... 




Anders: Tr. Coll. Phys., Philadel- 
phia, 1902. 


3 




23,000 






Anders: Idem. 


4 


3,750,000 


40,000 




.... 


Anders: Idem. 


5 


3,548,000 


4,500 


52 


.... 


McCallum; Journ. Exp Med., vol. 


6 


4,700,000 


5,000 


60 




Wright; Journ. Boston Soc. Med. 
Sc, April, 1900. 


7 


1,750,000 


Normal. 




.... 


Bradshaw: Med.-Chir. Trans., Lon- 
don, 1899, p. 251. 



Table CVIII. — Myxoma of the Liver. 



Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Per cent 

poly- 
nuclear. 


Per cent 

eosino- 

philes. 


Reporters. 


5.200,000 


12,000 


y 


56 


26(!) 


Tuffierand Milian- Loc. cit. 



For other sarcomata, see Tables CV. and CVI. 
On the whole, leucocytosis appears to be more constant and of 
rreater extent in sarcoma than in cancer. 



Qualitative Changes. 

1. The increase of polymorphonuclear leucocytes which we find 
in most forms of leucocytosis is not always present in sarcoma ' and 
seems to be less frequent than in cancer (see Cases 5, 11, 14, 
Table CV.). 

As in cancer, it may be present when no increase in the total 
leucocytes is to be found, and may be the only indication of any 
disease in the organism. 

2. A few cases are on record ^n which a large percentage of 
eosinophiles has been present. 

Eeinbach found 48 per cent of eosinophiles in a case of sarcoma 
of the neck with sloughing and ulcerative endocarditis, the percent- 

^ Palma (Deut. med. Woch., 1892) reports lymphocytosis in sarcoma. 



458 



SPECIAL PATHOLOGY OF THE BLOOD. 



age continuing over 40 for several weeks.' Autopsy showed sar- 
comatous nodules in the bone marrow. In another case, a tumor 
of the abdomen, the eosinophiles were 10.5 per cent, and in two 
others 8 per cent. 

A case of apparent sarcoma of the abdominal organs (no autop- 
sy) at the Massachusetts General Hospital in January, 1896, had 
12.4 per cent of eosinophiles. 

Such cases should certainly make us think of bone metastases, 
and Neusser speaks of osteosarcomata as being accompanied by 
eosinophilia, but the evidence is as yet fragmentary. 

3. Myelocytes. — Eeinbach's case just described had a low per- 
centage of myelocytes. 

The following cases illustrate the same point: 

Case I. is a case of sarcomatosis in a man in whom sarcomatous 
nodules were distributed all over the internal organs and in the skin. 
A differential count of 700 white cells showed in his case : 

Per cent. 

Typical myelocytes (over 15 //) 2 

Small myelocytes (under 15 //) 5 

Ljmphocj'tes 22 

Poly nuclear neutrophiles 70 

Eosinophiles 1 

The autopsy showed no special lesions in the spleen, glands, or 
bone marrow, except those due to the sarcomatous nodules. 

^ The full counts are as follows : 



April 4th, 1892. 


May 20th, 


1892. 


Red cells 5.396,000 


Red cells 

WhMe cells 


. .. 4.512.000 


White cells 120 000 (') 


52,000 


Haemoglobin 60 per cent. 


Haemoglobin 


. . . 55 per cent. 



DIFFEREXTIAIi COUNTS. 





April 4th. 1 May 1st. 


May 20th. 


May 26th. 


Polv. neut 


Per cent. 
48 
48 
2.7 

1 


Per cent. 
51 
46 
2.32 

.68 


Per cent. 

55 + 
42 
1.5 
.64 


Per cent. 

51 + 

44 + 

32 


Eosinophiles 


Lymphocvtes 


Mvelocvtes 


.8 







SARCOMA. 459 

Case II. — Sarcoma of the abdominal wall. A differential count 
of 800 cells showed : 

Per cent. 

Polynuclear neutrophiles 84. 

Lymphocytes 10. 5 

Large lymphocytes 5. 

Eosinophiles 2 

Myelocytes 3 

Case III. No. 5, Table CY. — Six hundred cells contained: 

Per cent. 

Polynuclear neutrophiles 71. 

Lymphocytes 16.2 

Eosinophiles 12.4 

Myelocytes 4 

Summary of Blood Changes in Malignant Disease. 

1. Small, slow-growing tumors and the early stages of all tu- 
mors may have no effect on the blood appreciable by our present 
methods of examination. 

2. In advanced cases the red corpuscles often become thin, light, 
and pale, and finally their number may be greatly decreased, the 
counts running sometimes as low as in pernicious anaemia. In this 
respect, as in others, sarcomata seem to injure the blood more than 
cancers. 

3. The color index is always beloAV 1, but is rarely as low as we 
find it in severe chlorosis. 

4. Normoblasts and megaloblasts (the latter being in the mi- 
nority) may occur, the former even in the absence of severe anaemia. 
Deformities in size and shape are common. 

5. Leucocytosis is present in the cachectic end-stages of many 
cases, but is frequently absent in small tumors of slow growth and 
without metastases. The polymorphonuclear cells are often rela- 
tively increased. 

6. Eibrin is not increased. 

Diagnostic Value. 

1. When we are dealing with an obscure, deep-seated disease, 
if hemorrhage is excluded, the presence of persistent leucocytosis 
suggests suppuration or malignant disease (rather than tuberculosis 
or syphilis, for example), and excludes any simply functional or 
liysterieal affection. The absence of leucocytosis, however, does not 



460 SPECIAL PATHOLOGV OF THE BLOOD. 

exclude malignant disease, though it makes suppuration very un- 
likely. 

2. Between malignant disease and suppuration — if the other 
signs and symptoms do not decide — there may be nothing in the 
blood to decide. In decided pyaemia we may get pyogenic cocci 
from the blood by culture, but a negative result would not exclude 
the suppurating focus. 

The absence of any increase of librin in the blood speaks against 
suppuration, and therefore in favor of malignant disease; but the 
presence of increased librin network is not decisive either way, as it 
may be met with in connection with neoplasms, though more com- 
mon in suppuration. 

3. Between malignant disease and hemorrhage a marked anae- 
mia favors the latter, provided the case is a recent one; for the 
anaiinia of malignant disease is comparatively slow to develop. The 
leucocytes give no help. 

4. Between cancer and ulcer of the stomach, if there lias been 
no recent bemorrluige, leucocytosis favors cancer; but its nhseure 
is of no weight either way. 

The haemoglobin is said to decrease steadily in cancer, while in 
ulcer it tends to return toward normal after the cessation of hemor- 
rliage. 

The presence and persistence of digestion leucocytosis speak 
against cancer, and its absence in favor of cancer. It must be 
remembered, however, that any variety of catarrh or dilatation 
(should such be present) can also prevent digestion leucocytosis, 
and that the latter is not invariably present even in health. 

5. Between cancer of the liver or bile ducts on the one hand and 
simple gall-stone colic or gall-stone obstruction on the other, the 
presence of leucocytosis favors cancer. As usual, however, its ab- 
sence does not exclude cancer, and we must bear in mind that gall 
stones with cholangitis may raise the leucocyte count as much as 
cancer. Simple cysts or echinococcus cysts cause no leucocytosis, 
nor does syphilis of the liver. 

6. The appearance in the blood of large numbers of eosinophiles, 
myelocytes, and nucleated corpuscles during the course of a malig- 
nant disease suggests a bone metastasis. 

7. When a leucocytosis which has disappeared after removal of 
a neoplasm reappears, we may expect recurrence of the growth 
shortly. 



SARCOMA. 461 

8. A steadily iDcreasing leucocytosis in a case of malignant dis- 
ease points to a rapidly growing tumor or to the occurrence of 
metastasis. 

9. Between malignant disease and pernicious anaemia, the diag- 
nosis rests on the following points : 

(a) Color index and volume index low in malignant, apt to be 
high in pernicious ansemia, 

(b) Leucocytes often increased in malignant, diminished in 
pernicious ansemia. 

(c) Lymphocytes often relatively decreased in malignant, in- 
creased in pernicious anaemia. 

(d) Average size of red cells often decreased in malignant, and 
often increased in pernicious anaemia. 

(e) If nucleated red corpuscles are present the normoblasts are 
in a majority in malignant disease, and in a minority in pernicious 
anaemia. 

10. The presence of leucocytosis is against the benignness of 
any tumor. 

11. When no actual increase of leucocytes is present, an in- 
creased percentage of the polymorphonuclear variety among those 
present may have the same significance as a leucocytosis. 



CHAPTER XI. 

BLOOD PARASITES. 

EXAMINATION FOR THE MALARIAL PARASITE AND ITS 

PRODUCTS. 

I. Time for Examination. 

It is often stated that the organism is most easily found during 
the chilL But this is not the writer's experience. During a chill 
it is often difficult and sometimes impossible to find the o ganisms. 
Eight hours before or after a chill is the most favorable time 
(Thayer), although parasites have been found as late as forty-eiglit 
hours after the last chill. During the chill many organisms retire 
to the internal organs. 

The number of organisms varies a great deal. In some cases 
they are present in every field of a one- twelfth immersion lens, 
while in others we may find only one after an hour or more of pa- 
tient search. In some cases of coma Ewing had to search one and 
two hours before finding a single parasite. In the majority of the 
cases occurring near Boston, it needs but a few minutes' search to 
find parasites if the blood be taken within twelve hours before or 
after a chill, and provided no quinine has been lately given. Occa- 
sionally in mild cases the organisms are very scanty; and it may be 
almost impossible to find any. I agree with Theobald Smith and 
Ewing that when the parasites are scarce, especially when they are 
of the small unpigmented form, a prolonged search through fresh 
blood frequently proves negative, although a few minutes suffices 
for the discovery of one or more minute parasites in the stained 
specimen. 

II. Method of Examination. 
(a) Fresh Blood. 

A slide of fresh blood is prepared as described on pages 6-8 
and examined with a one-twelfth immersion lens.' Lower powers 

^ In cold weather both slide and cover should be warmed before using. In- 
deed this is always well, as it makes the corpuscles spread better. 



PARASITES OF TERTIAN FEVER. 

(WRIGHT'S Modification of Leischmann's Stain.) 

Photographs by Wright & Brown, Clinico-Pathological 
Laboratory, Mass. General Hospital. 



PLATE V. 




Fig. 1.— The spotted cell on the rl^ht is an erythrocyte containing a young tertian organism 
and overlapped at its margin by a blood-plate. The dark mass overlying the cell at the ex- 
treme left is also a blood-plate. 




Fig. 2.— Two red cells showing granular degeneration. That on the right contains one, that 
on the left two, young tertian parasites. The chromatin bodies appear as rounded black 
spots. 





Fig. 3.— Young Tertian Parasite. 



Fig. 4.— Above, a tertian parasite about 
six hours old. Below, a blood-plate 
overlying a red cell. 




Fig. 5.— Tertian Parasite about ten hours old. 
In this and in the next figure the granular de- 
generation of the red cell is very marked. 



Fig. 



6.— Red Cell considerably enlarged, 
containing two young tertian para- 



TERTIAN PARASITES ABOUT HALF GROWN 

And Occupying Enlarged and Degenerated Erythrocytes. 
(Stained as in Plate V.) In No. 2 Two Blood-Plates 
Appear Among the Cells. 

Photographs by Wright & Brown, from the Clinico-rathological 
Laboratory, INIass. General Hospital. 



PLATE VI, 




FIG. 1. 




Fig. 3. 




Fig. 3. 




Fig. 4. 



MALARIAL PARASITES. 463 

should not be used, although in skilful hands they are often suifi- 
cient. Portions of the slide in which the corpuscles do not overlie 
each other should be chosen for examination. As we pass the slide 
along beneath the lens it is well to be on the lookout for any s/j/e- 
cially large or specially pale corpuscle. Such a one will catch the eye 
if we are on the watch for it, even though the slide is being passed 
along very rapidly, and all such should be carefully examined. 

Another thing to watch for is anything black or dark brown. If 
the slide is not perfectly clean, or if the cover glass has touched the 
skin in collecting the blood, there will often be black spots which 
make us pull up short and examine, only to find that they are bits 
of dirt. This loses time, and hence, as above noted, the importance 
of care and cleanliness in the earlier stages of the process. 

Besides any strikingly pale or swollen corpuscle or any black 
dots, Ave should be on the lookout for any movements in the field 
The movements of Muller's "blood-dust" (see page 58) are often 
mistaken by beginners for those of the malarial organism. Their 
greatly smaller size and extracorpuscular position serve to distin- 
guish them in most cases. T have sometimes thought I saw pig- 
ment in these bodies. If, as Stokes believes, the "blood-dust" is 
derived from the leucocytes, it is possible that they might carry out 
with them some pigment ingested by the leucocyte. 

Flagellate bodies may be studied in fresh specimens, if possible, 
on a warm stage. Usually they appear only after the lapse of from 
ten to twenty minutes from the larger tertian or ovoid sestivo-autum- 
nal organisms. The addition of a little water or salt solution may 
facilitate the escape of the parasite from the red cell and the forma- 
tion of flagella. 

Ewing finds that a moist chamber may be secured in a Petri 
dish with tightly fitting vaselined cover. Wet blotting-paper placed 
in the dish furnishes the necessary moisture. Specimens spread on 
slides or covers may be kept moist for ten to twenty minutes in 
such dishes, and flagellation proceeds with moderate rapidity 

A simple method is as follows : Cut an opening one-half by one 
inch in a piece of thick blotting-paper and moisten the paper in 
hot water. Spread two glass slides rather thickly with fresh blood, 
lay the blotting-paper on one slide, cover the cut opening by the 
other, specimen side down, and slip a rubber band about both. 
After fifteen or twenty minutes the slides and paper may be sepa- 
rated and the two specimens dried. 



464 SPECIAL PATHOLOGY OF THE BLOOD. 

The Malarial Oryonisin. — It practically is never to be seen out- 
side the corpuscle. Most malarial organisms are to be found within 
the corpuscle, and only there.' 

For those who have not examined man}^ specimens of malarial 
blood it is a very difficult thing to find the organism in the early 
stages of its growth, and the number of mistakes in diagnosis is 
very large. I always look with great suspicion on any report of 
malarial blood as containing onhj " hyaline forms " in fresh speci- 
mens. 

In the later stages, when the organism has become well pig- 
mented, there is nothing that at all resembles it, and those who 
have seen and watched it a few times can hardly mistake anything 
else for it. Not so with the so-called ^' hyaline " or youngest form 
of the organism. Personally I think the name "hyaline bodies" 
is responsible for a part of the mistakes. We are led to expect 
something more shiny and refractile than the organism really is, 
and so are misled by the brilliant white circles to l)e found at the 
centre of many normal corpuscles under certain conditions of light 
and partial drying up. Time and again I have been asked to look 
at malarial organisms (always the "hyaline " forms), and found 
nothing more than one of these effects of light which can be found 
in any normal blood, if the conditions are right. 

As soon as the organism gets any pigment (and there are very 
few times in the cycle of a malarial case when there are not some 
l)igmented organisms present), the active rapid motion of the black 
pigment dots is unlike anything else seen in the l)lood, and when 
once recognized can never be forgotten or mistaken. It is only 
when the pigment has ceased moving (owing to the death of the 
organism) that the differentiation between dirt and malarial pig- 
ment becomes difficult. 

Almost all stages of the growth of the plasmodium which we 
can watch in the blood drawn from the peripheral circulation take 
place within the corpuscle. It is true that as the pigmented organ- 
ism gets toward its full growth, and before the granules have be- 
gun to gather at the centre, we iwaj find it very difficult to see any 
trace of corpuscle substance around the margin of the plasmodium. 
Sometimes we see a ring of non-pigmented glistening white sub- 
stance outside the moving black dots (see Fig. 2, 7, Plate I.) stand- 

' Except degenerate forms, free flagellae, and spores at the moment of seg 
mentation {rarely to be seen). Crescents and ovoid bodies are intracelhilar. 



PLATE C. 

The numbers correspond approximate!}' with the stages of development. 
In Nos. ? to 15 tlie chromatin is divided more and more and the amount of 
blackish pigment increases. 

No. 4 shows the pink stippling often seen in infected erythrocytes; al)ove 
No. 5 is a blue-stippled erythrocyte of the type seen in various ansemias. 

In No. 14- (presegmenting stage) the new nuiltiple nuclei of the future 
segments are seen. 

No. 15, a segmenting body, shows no sign of the red cell. One segment 
was fixed at some distance from the main group as if on the way io attack 
another red corpuscle. 



Examination ofthe Blood. 



Plate C. 



1 



2 



^ 



.a 



s 



*A ^ 






mi. <9 



<. 20 



12 



13 



Jl 



[^^V 



mi 



M 



.'f-j 



Mary W, Rowley, del 



The Parasite ofTertiaw Malaria. 

(Wight's TTiodificatioTi of leisTLman's stain..) 



MALARIAL PARASITES. 465 

ing out Ikjld (igainst tlie darle.r plasinu , This I suppose to be tlie 
remains of the corpuscle. It is not described or pictured in the 
standard Avorks on the subject. 

Occasionally we do find pigmented bodies wlioll}' outside the 
corpuscle, either partly or fully grown. In the intracorpuscular 
forms the distinction between plasmodiuni and corpuscle substance 





Fig. 32.— Flagellate Malarial Organisms. (After Thayer.) 

is not, I think, so shar}) and clear as one would be led to expect 
from the plates in standard works. With average eyes and lenses 
the outline of the organism, as distinguished both from its pigment 
granules and the surrounding corpuscle, is not easy to see. 

But all these difficulties as well as those about recognizing the 
" h3^aline forms " on which I expatiated in earlier editions of this 
book, have now been abolished for me, and should be for all stu- 
dents of malarial blood, by the introduction of a simple, ciuick, and 
reliable method of getting the Romanowsky stain. I refer to Leish- 
man's stain as modified by Wright (see page 41). For diagnos- 
tic purposes I never use the fresh blood now, and I am convinced 
that by using the stained film specimen in every case I recognize 
cases of malaria that used to escape me before. For purposes of 
study the fresh blood is important — but not, in my opinion, for 
diagnosis. The method of staining is precisely that used for ordi- 
nary differential leucocyte counts and has been already described. 

{I)) Appearance of Stained Specimens. 

For the main points the reader is referred to Plates I and C, 
and the descriptions accompanying tliem ; some additional details 
are here added. 

The youngest form of the tertian pjo/rasite seen in the red cell is 

identical in appearance with the spore of the parent rosette. It is 

a compact spheroidal, or slightly oval, or irregular body, about 2 //. 

in diameter. It shows an outer rim of basophilic protoplasm en- 

30 



466 SPECIAL PATHOLOGY OF THE BLOOD. 

closing a single large nu(.'lear body, which is achroniic to methylene 
blue, but stains readily in hsematoxylon or by Nocht's method, and 
which is usually enclosed or accompanied by a clear achromatic sulj- 
stance, termed by Gautier ''the milky zone." 

In the fresh condition these bodies are noticeably refractive^, 
especially the nucleus, change their ])osition Init rarely tlieir shape, 
and are never pigmented. 

The youngest tertian riiuj : ^Vithin a few hours after the chill 
tlie parasite is usually found to have assumed a somewhat charac- 
teristic ring shape. These bodies measure from 3-4 // in diameter, 
and there is not much increase in bulk for six or eiglit hours. The 
tertian ring is rarely as geometrical or delicate as the sestivo-autum- 
nal signet ring. The nuclear body of the tertian ring is its most 
characteristic feature, appearing as a rather large, achromatic, 
liighly refractive body, after metliylene l^lue, but staining intensely 
crimson with Leishman's stain. 

Comparison of the Tertian and ^^stioo- autumnal Biinjs. 

I abstract here Swing's admirable description: 

1. The shape and contour of the tertian ring is usually coarse and 
irregular, but the sestivo-autumnal ring is geometrically circular, 
more delicate, with extremely fine bow, and usually with a typical 
signet-like swelling. 

2. One or two grains of pigment are almost invariably found in 
the early tertian ring, but are with nearly equal constancy absent 
from the sestivo-autumnal signet ring. 

3. The tertian ring is usually pigmented before the chromatin 
becomes subdivided, wdiile the chromatin of the a^stivo-autumnal 
ring is always subdivided before the appearance of pigment. 

4. The infected cell is usually swollen from the moment of 
infection by the tertian spore, and commonly shrunken when har- 
boring the sestivo-autumnal ring. 

Tlie Tertian Farasite — Later Stages. 

Large tertian rings : After a period of six to eight hours the 
ring is usually found to have developed an outgrowth wdiich is 
actively amoeboid in the fresh condition and appears in stained 
specimens as a tongue-like protrusion or turban-shaped mass at- 
tached to one segment of the ring. The nuclear body meanwhile 



STAINED AS IN PLATES V. AND VI. 

i*hotogTaphs by Wright & Brown, Cli 
Laboratory, Mass. General J 



PLATE VII. 



-Pathological 
.ital. 





Fig. 1.— Above, on Right, a Half-grown Ter- 
tian Parasite. On left two blood -plates, one 
overlying a red cell. 



Fig. 3. Tertian Parasite, about forty- 
hours old. The chromatin, in the form 
of fine granules, is within the open space 
in the upper left corner of the parasite. 





Fig. 3.— Same as Fig. 



Fig. 4. — Well-developed Tertian 
Parasite. The chromatin appears 
as an irregular-shaped dark mass 
containing open spaces. 





Fig. 5.— Same as Fig. 4. 



FIG. 6.— Tertian Parasite just before Seg- 
mentation. The chromatin (dark oval 
masses) is distributed throughout the 
parasite. The pigment (smaller dark 
points) is collected just to the left of the 
centre. 



MALARIAL PARASITES. 467 

increases slightly in size, projecting into the ring, and the chromatin 
divides into several large granules. 

At this period occurs the greatest amoeboid activity of the- para- 
site, and in some severe infections the organism may be found fixed 
in the height of its amceboid excursions. There the ring persists^ 
but the body of the parasite is strung out into a number of slender 
threads with nodal thickenings. 

Tertian splierokhjl hodks : During the second quarter of the 
cycle, the body and nucleus of the parasite develop rapidly in size, 
amoeboid motion and figures gradually diminish, and pigment is 
abundantly deposited in the form of dark brown or yellowish grains, 
showing in the fresh state active vibratory motion. The cell in- 
creases in size and its haemoglobin diminishes. Toward the end of 
twenty-four hours or possibly somewhat later, the parasite occupies 
three-fourths of the swollen cell, in the form of a spheroidal or 
elliptical, homogeneous body, the outer portion of which contains 
most of the pigment. 

Fidl-groicn tertian ijaraslte : The third quarter of the cycle is 
occupied by tlie continued growth of the parasite in the form of a 
large homogeneous, richly pigmented bod}", which finally occupies 
at least four-fifths of the swollen cell. 

Fresegmentincj bodies usually begin to appear in the blood eight 
to ten hours before the chill. The pigment is gathered in a reduced 
number of coarse grains or spindles which lie in the body of the 
parasite, in a position determined by that of the new multiple 
nuclei (crimson stained). 

Tertian rosettes are usually seen in the circulation three or four 
hours before the chill, most abundantly just before the chill, rapidl\' 
disappearing after the chill. 

The jEstifo- autumnal Parasite. 

The earliest form of the a^st loo- autumnal xjarasite is usually to 
be distinguished from the tertian by the shrinkage of the cell, and 
by its low refractive index; it is never pigmented. 

The cestivo- autumnal signet ring is a very characteristic shape as- 
sumed by the parasite at a very early period. It is noted that in some 
cases the rings fail to exhibit this thickening but remain of a uni- 
form but very fine calibre throughout. Multiple infection with the 
young rings is very common; three parasites are often found in tlie 
same red cell, and occasionally four. The signet-ring forms fre- 



4G8 SPECIAL PATHOLOGY OF THE BLOOD. 

queiitly reach a diameter of 4 // ; beyond this size, when persisting 
in the 2>eriplieral blood, the growth of the parasite produces an 
irre<4iihir body in which the outline of the ring becomes more or less 
obscure. The full developnuMit of the large signet rings appears to 
require about twenty-four licjurs. In the majoritj' of cases the ring 
forms seen in the peripheral blood fail to show any trace of pigment. 

The later forms of the n'stlro-dntitinnaJ parasite are rather rarely 
seen in the peripheral circulation. 

The crescent ic bodies : On the fourth to sixth days of an}' but ini- 
tial })aroxysms of the aestivo-autunnial infection the peripheral blood 
may contain red cells infected by spheroidal, oval, elliptical, or 
small crescentic bodies which represent the early forms of the sexual 
cycU^ of the parasite. The relation of these forms to the young 
anueba is not clear. A renniant of haemogloVjin surrounds the cres- 
cent. The membrane or thickened outer border of the red cell i> 
closely api)lied about the convex side of the blue-stained crescent, 
while across the concavity it stretches loosely like a halter. 

hi the centre of tlie crescent is a sharply marked, light-blue 
staining or achromatic area of variable size, containing the pink- 
stained chromatin, and usualh' also the pigment. 

The long persistence of crescents in the blood and their resist- 
ance to (piinine are matters of common clinical observation. 

The Quartan Parasite. 

I have never seen a live parasite of this type. The accompany- 
ing drawings (see Plate D) are from a case of triple quartan infec- 
tion, the specimen being kindty loaned me by Dr. Futcher of Balti- 
more. I shall attempt no description bej'ond that accompanying 
the plate. 

Dr. J. H. Wright has kindly permitted the use of the accompa- 
nying photographs of the malarial parasites (see Plates V., VI., 
YII., VIII., and IX.). 

Flagellate bodies : When blood containing crescents is allowed 
to stand in the air or under a cover glass for a few moments some 
of the crescents slowly assume the spheroidal form, active vibratory 
oscillations of pigment granules begin, and soon, from one or more 
points, pseudopodia shoot out with active lashing movements. 
These flagella continue their movements for some time, changing 
their position actively, their shape slowly, while some may be seen 
to break off from the body and swim off through the plasma. 



/ESTIVO-AUTUMNAL PARASITES. 

(WRIGHT'S Modification of Leischmann's Stain.) 

Photographs by Wright & Brown, Clinieo-Pathological 
Laboratory, Mass. General Hospital. 



PLATE VIII 




Fig. 1.— On the left a single young gestivo-autumnal parasite. On the right two within a 
single cell. Chromatin appears in small, dark, rounded masses. 




Fig. 3.— Two testivo-autumnal parasites in one cell. In one the chromatin is divided. 



Fig. 3.— Jilstivo-autumnal parasite, somewhat more developed than in t'le preceding figure. 




Fig. 4.— Above, a blood-plate. Below, on the right, a young sestivo-autumnal parasite. On 

the left a "crescent." 



i 



MALARIAL PARASITES 



469 



Tertian flagellate bodies de- 
velop from the full-grown ter- 
tian parasites in much the same 
way as from the crescents. 
Quartan parasites develop fla- 
gellate bodies very similar i\\ 
appearance to those of tlie 
sestivo- autumnal type. The 
flagellse are about two or three 
times as long as a red corpuscle 
and one-sixth or one-eighth as 
wide. Sometimes there is pig- 
ment dotted along the flagellum 
itself, and then we can nmke it 
out more easily. Its distal end 
is especially apt to be pig- 
mented, and by the help of this 
pigment we make out that it is 
bulbous, while similar swell- 
ings can sometimes be seen at 
other points along the flagellum 
(see Fig. .33). As the pig- 
mented end is sometimes all 
that we can see of it, this gives 
rise to the appearance of a very 
small, actively locomotive pig- 
mented body free among the 
corpuscles, and its course may 
be followed through several 
fields. 

When the flagella have 
ceased moving, their presence 
is generally detected, if at all, 
by an irregular line of pigment 
dots about 20 ij. long, which will 
be shown by careful focussing 
to be contained within a nearly 
transparent membrane. 

Very often we find a leuco- 
cyte in process of closing round 



/ 



\ 



^ 




/ 





Fig. 33.— Flagellfltc Mahiiial Oi'iaiilsni 
(After MaiisoiTs iili(itcM.M';n lis.) 



470 SPECIAL PATHOLOGY OF THE BLOOD. 

tlie flagellated x)arasite. Manson has lately succeeded in staining the 
flagellse, and the accompanying photographs are from his stained 
specimens. 

Pigmented leucocytes, containing the whole or part of malarial 
oiganisms or simply blocks or granules of black pigment, are usu- 
ally to be found in the blood near the time of the chill. The pig- 
ment is to be carefully distinguished from the granules present in 
most leucocytes, which in certain lights look quite dark even if un- 
stained, dark enough to be mistaken for pigment by the untrained 
eye. Careful focussing and changing the light will easily deter- 
mine which we are dealing with, provided we are familiar with the 
appearances of leucocytes in the fresh unstained blood. In certain 
forms of the disease in which the organisms themselves retire to 
the internal organs, the presence of pigmented leucocj'tes may be 
the only evidence of the disease to be found in the peripheral blood 
and is therefore of the greatest importance. 

How long after a chill the organisms may still be found in the 
peripheral blood is difficult to decide, but certainly they can be 
found any time within twenty-four hours after the last chill, unless 
quinine has been given, and sometimes even if it has been given. 

I have not attempted to discuss the interpretation of the differ- 
ent forms now believed to be sexual, or of the so-called '' conjugat- 
ing cycle " of the tertian parasite. I have also excluded all descrip- 
tion of the life of malarial parasites in the mosquito and of their 
transmission by this insect to human beings. These tempting sub- 
jects are necessarily excluded by the x^lan of this book as a clinical 
treatise for diagnostic purposes. 

Other Changes ix the Blood. 

Bed Corpuscles. — The following is from Thayer's monograph: 
"A reduction in red corpuscles follows each paroxysm; these 
reductions are more marked after the early paroxysms than after 
those occurring later. When a certain degree of anaemia has been 
reached the losses per paroxj'sm are much less. When the number 
of corpuscles is reduced to 2,000,000 or 1,000,000 there is little 
tendency toward a further fall; sometimes there may be slight rises 
•in the curve between the parox^^sms; often, however, the number 
of corpuscles remains stationary for weeks. In pernicious cases 
the number of corpuscles may fall between paroxysms." Kelsch 
has seen the count decrease to as small number as 583,000 -pev cubic 



PLATE D. 

Fig. 1.— The Quartan Parasite. 

a, a, (I, etc.. Youugest forms. 

b, h and c. c, Maturei- forms. 
d, d, Presegmenting forms. 

<-. Segmenting parasite (note the small number of segments com- 
pared with the corresponding stage of the tertian parasite). 

Pigment and chromatin are more scattered tlian in tiie other forms of ma- 
larial parasite. The infected red cell is not enlarged. 
Fig. 2.— The .Estivo-Aiitumnal Parasite. 
1, ~:, S, 4, Early ring forms. 
5, G, S, Maturer forms. 
7, Elongated form (transition to crescent?). 

9, 11, Crescents. 

10, 12, 13, U, 15. O voids. 

These are the only forms found in peripheral blood. Segmenting bodies 
occur in internal organs. 



Examination ofthe Blood. 



Plate D. 






C c 



^ .±^ c 



£jJt> 



d 



-.... c 






A'rsi-^;-vVP, 



ryvY. Rowley, del . 



~ig.l. TsE riASAsiTE OF Quartan Kalahia. 

(Vfcights modificailoTi of Leisl-jra^i^ stair. .) 



^fer 



^' 



-. 7 



10 



■'-^i 



/"Mi 
/J 

7J 



^11 



m 



MhTyW-KoyHey, del . 



1^.2. iHE Parasite of Aesttvo — AuruMtiAL Mai/jha. 

("Vfeight's TtiodlilcatloTi of leisTimarife stain.) 



GeoHWalker i Co,IiflwBo5ton. 



MALARIAL PARASITES. 471 

millimetre. The diminution is greater the longer the disease lasts 
and the more intense its manifestations are. 

During the paroxysms, particularly the earlier ones, the red cells 
tend to increase in number. In tertian and quartan fevers there is 
a rapid and almost complete restitution of the corpuscles during the 
afebrile period. 

In Swing's Montauk series, there were "no less than nineteen 
cases in which the changes of the progressive pernicious type had 
been established in a period not longer than ten weeks. . . . 
There can be no doubt that the tendency of the aestivo-autumnal 
parasite is to be massed in the bone marrow. The excessive de- 
mands on red-cell production render pernicious malaria an extremely 
favorable condition for this disturbance of the marrow and specific 
megaloblastic changes." 

In sestivo-autumnal fevers the number of red cells is in inverse 
relation to the number of young parasites, but crescentic bodies 
seem to have no influence on the number of red cells. 

Bignami and Dionisi distinguish three types of post-malarial 
ansemia : 

1. Ordinary secondary anaemia, with leucopenia; such cases usu- 
ally end in recovery. 

2. Ansemia practically identical with pernicious anaemia, megalo- 
blasts being present, and ending fatally. 

3. Anaemias which are progressive, because the bone marrow 
cannot compensate for the losses of corpuscles. 

The rapidity of the diminution in red cells may be very great. 
Kelsch's count of 583,000 cells per cubic millimetre, mentioned 
above, was after thirty days' illness. Grawitz has seen a loss of 
4,000,000 cells in six days. 

Qualitative changes are those of severe secondary anaemia, anom- 
alies of staining reaction, deformities in size and shape, normo- 
blasts, occasional megaloblasts in the worst cases, motility in the 
"pale, ghostly" cells. 

Koemoglohin. — The loss of haemoglobin bears usually a direct re- 
lation to the number of parasites in the blood. As a rule, the cor- 
puscles and haemoglobin are diminished proportionally (color index 
= 1), but sometimes the haemoglobin is reduced disproportionately. 
On the other hand Delaney ' has often found the color index above 
normal. 

1 Delaney: Brit. Med. Jour., March 28th, 1903. 



472 SPECIAL PATHOLOGY OF THE BLOOD. 

In convalescence the restitution of haemoglobin is often incom- 
plete; persons living in malarial districts have often a slightly 
smaller percentage of haemoglobin than those living elsewhere. 

The rapid diminution in tlie red cells is a valuable point in dif- 
ferential diagnosis between malaria and typhoid or pneumonia. 

White Ceils. — The number of leucocytes is usually subnormal, 
but a slight increase is shown at the beginning of the paroxj-sm. 
J^'ollowing this increase there is a rapid decrease coutinuing through- 
out the paroxysm. The smallest number of leucocytes is to be seen 
at the end of the paroxysm when the temperature is subnormal. 
From this time it shows a gradual increase until the beginning of 
the next attack (Billings). 

In a general way the white cells follow the same course as do 
the red. 

The differential count shows a relative lymphocytosis whenever 
the white cells are subnormal, the larger forms of 13-mphocytes being 
especially numerous, while the polymorphonuclear cells and eosino- 
philes are scanty. Great stress has lately been laid by several 
English observers upon an increase in the i)ercentage of large mono- 
nuclear cells (large lymphocytes) in malaria as a point of differen- 
tial diagnostic value between malaria and other fevers — especially 
typhoid. Stephens and Christopher,' Tiirck,^ Rogers,^ Melland,* 
Delaney,^ and others have substantially agreed in their findings. 
They state that: 

1. In malaria (between paroxysms) the leucocytes are often Ije- 
low 2,000; in typhoid rarely so. 

2. In malaria the large mononuclear forms are frequently be- 
tween 12 and 30 j)er cent. In typhoid between 2 and 6 per cent. 

3. In malaria the small lymphocytes are not increased, while in 
typhoid they are often 40 per cent or more. 

4. In malaria myelocytes and stimulation forms are often present 
(1 to 5 per cent) ; in typhoid rarely. (These conclusions refer to and 
hold good for the blood of adults only.) 

In the severer aestivo-autumnal paroxysms Kelsch found that 
the increase in the total count of leucocytes was often due to a 

^ Stephens and Christopher: Malaria Commission of Royal Society. 5th re- 
port, 1901. 

•*Turck: Loc. cit. ^j^ogers: Brit. Med. Jour., April 5th, 1902. 

•^Melland: Ibidem, September 27th, 1903. 
^Delany: Brit. Med. Jour., March 28th, 1903. 



TERTIAN ORGANISMS. 

(After Wright & Brown. ) Stained with eosin and methylene blue. 



PLATE IX. 




Fig. 1.— Young Non-pigment- 
ed Form (Tertian). 






Fig. 2.— At the left, a young, pigmented 
tertian parasite. On the right, a:n adult 
tertian parasite. Rod - shaped pigment. 
The chromatin not stained. 





Fig. 3.— Two pigmented ter- 
tian parasites in one cor- 
puscle. 



Fig. 4.— An adult tertian parasite with central vacuole 
and rod-shaped pigment in a distorted red blood 
corpuscle at the left of the figure. At the right of 
the figure an adult parasite with its pigment gathered 
together in clumps. This is a tertian parasite in the 
early stage of segmentation. The dark spots at the 
periphery of the parasite represent the remains of the 
red blood corpuscle which it has invaded. 




Fig. 5.— An adult tertian parasite in the 
same stage as the one last mentioned, 
with its pigment collected in a more com- 
pact manner at its central part. The irreg- 
ular dark zone at Its periphery is the re- 
mains of the red blood corpuscle in which 
the parasite has developed. 




Fig. 6.— Comnleted segmentation of a tertian 
parasite. Each of the dark rounded bodies 
represents a young parasite. The pigment 
of the parasite from which they are derived 
is shown, as well as the faint outlines of the 
red blood corpuscle in which they are con- 
tained. 



PLATE X. 





Fig. 7.— a young tertian 
panisire and an adult 
parasite with a vacuole, in 
one red blood corpuscle. 



Fig. 8.-Same as Fi<?. 6. 




Fig. 9.— Crescentic form of the avstivo-autumnal parasite in 
a red biood corpuscle, whicli is much distorted by it. The 
pigment is seen in the centre of the parasite in the form of 
rods. 



Fig. 10.— Same as Fig. 




Fig. 11.— Ovoid form of the 
asstivo - autumnal para- 
site distending a red 
blood corpuscle. A por- 
tion of the corpuscle pro- 
jects above the parasite, 
and is much distorted. 
The dark line around the 
parasite also repr'esents 
the remnants of the cor- 
puscle. 




Fig. 12.— In the right of the figure is a crescentic parasite. 
In this photograph the blue-stained parasite is made to 
appear darker than the eosin-stained red blood coi-pus- 
cles, by changing the character of the light used for 
the illumination of the specimen. The deeper staining of 
the poles of the parasite is shown. In the left of the 
figure a tertian parasite in a red blood corpuscle is 
shown. There was, therefore, a double infection in this 



MALARIAL H^MOGLOBIN^MIA. 473 

marked lymphocytosis; this was also observed by Ewing. The ex- 
tent of the leucocytosis varies between 10,000 and 35,000 cells, the 
latter having been observed by Kelsch shortly before death in a 
comatose patient. In similar cases, often comatose, Delaney {loc. 
cit.) has seen leucocytosis of 38,000 and 14,300, and Manson records 
30,000 in some '* pernicious " cases. 

Ziemann {DeAit. wed. fVoc/i., November 22d, 1900) has recently 
made the interesting observation that in cases of malarial infection 
occurring in negroes with spontaneous recovery, a marked leucocy- 
tosis may occur. In the summer of 1902 two cases presenting ex- 
actly tliese conditions came under my observation; the fever was 
of the tertian type with abundant and characteristic parasites, the 
leucocytes ranged between 19,000 and 25,000 for twenty-four hours. 
No other disease could be found to account for it. No quinine was 
given and spontaneous recovery followed. 

In post-malarial anaemia Billings, Thayer, and Da Costa have 
found quite marked leucocytosis. 

Grawitz and others have noticed an increase of eosinophiles in 
post-malarial anaemia. I have frequently found small percentages 
of myelocytes, three per cent being tlie highest in my experience. 

MALi^RIAL H^EMOGLOBIN^MIA. 

During the paroxysms of this form of the disease, the number of 
the red cells is much diminished, rouleaux are not formed, marked 
poikilocytosis with nucleated forms is observed. The leucocytes 
are increased. The regeneration is very swift, from twenty-four to 
forty-eight hours being usually sufficient to re-establish normal con- 
ditions. 

Typhoid Fever and Malaria. 

'' After the first week when the typhoid fever has become fully 
established, active sporulation of malarial parasites is extremely 
rare " (Ewing) . 



CHAPTER XII. 
DISEASES DUE TO ANIMAL PARASITES. 

FILARIASIS. 

Although inost commonly found in tropical countries, one spe- 
cies of the filaria sanguinis liominis is not very uncommonly found 
in various parts of the United States. Any case of chylous urine, 
lymph scrotum, tumor of the groin, or elephantiasis should lead 
us to make a careful examination of the blood for the filaria. There 
are at least .six species of filaria, one of which is present in the 




Fig. 84.— Tlif i-ilaija >:iii<;niiiis Muiiijiiis. Tlit- ]it-ao. . , .: . ~ .. ^;jt of the CUt, 

tlie tail at the left, lustantaneous photomicrograph. Four hundred diameters magnifloation. 

blood chiefly at night, another chiefly during the daytime, and 
another continuously. In Uganda and parts of India a majority of 
all natives carry the filarise as "commensals " or messmates; we can 
hardly call them parasites since both filaria and native usually re- 
main in good health. Only tlie filaria oiocturna has thus far been 
seen in America (Fig. 34). 

In examining for the filaria a slide of the fresh blood is prepared 
in the usual way, hut after 8:30 o^ clock in the evening,^ and examined 
at once. Lothrop and Pratt " counted hourly the number of em- 
bryos per cubic centimetre by drawing blood to the mark 1 in a 

^ In persons who sleep in the daytime and work at night the habits of the 
filaria are said to become reversed, so that it appears in the peripheral circula- 
tion chiefly in the daytime, and is to be looked for then. 

*' Lothrop and Pratt : American Jour, of Med. So. , November, 1900. 



FILARIASIS. 



475 



Thoma-Zeiss pipette, blowing it out on a cover slip and counting the 
number of embryos in this drop (whose size could be estimated). By 
this means they obtained the accompanying chart, showing the in- 
crease and decrease of filaria in the peripheral blood. One slide 
made at midnight contained twenty-five filarise — the equivalent of 



TLC 


^r. 7. 


?• 6 6 10 mii 


r:vf\iZ 4 6 8 1 


nr 


1^0 












/ 


\ 


















/ 


\, 


/ 


\ 




















/ 


\ 


/ 


\ 












800 

600 
400 

200 








/ 


^ 


f 


\ 


/ 


\ 














/ 








/ 


\ 
























\ 












/ 


1 










\ 










.^ 


/ 












\ 




.^ 











Fig. 35.— Number of Filanse in Cutaneous Circulation, 

2,100 per cubic centimetre, or about 6,800,000 in the whole mass 
of the circulating blood, supposing them to have been equall}^ dis- 
tributed, as they probably are not. The embryo of this parasite 
(which is what we find in the human blood) is from one-ninetieth 
to one-seventieth of an inch in length — i.e., about fifty times the 
diameter of a red cell, and about the width of a red corpuscle. 
Seen in the blood it retains its vitality and motile power for a con- 
siderable time, so that its motions may continue a week or more 
between slide and covers glass. Cold has little effect upon it, even 
freezing temperature failing to do more than make the movements 
slower. 

A distinction can generally be made out between the embryo 
proper and its sheath (see Fig. 36). From this sheath the embryo 
escapes when in the blood of the mosquito, which insect acts not in- 
frequently as intermediary host and conveys the parasite indirectly 
from man to man through the medium of water. After sucking in 
the organism with the blood the mosquito lays its eggs and dies in 
some neighboring pond or stream whence the filaria again gains 
access to men. 

It is a long, slender, snake-like, gracefully shaped worm, and 
when alive its activity is so great that measurements and observa- 



476 SPECIAL PATHOLOGY OF THE BLOOD. 

tions of its structure cannot be made till it is paralyzed by approach- 
ing death (Fig. 37). 

Posteriorly it tapers for one-fifth its length down to a very sharp 
point. The extreme end of the tail often looks as if articulated, fur 
it does not harmonize with the general curve of the body, but lies 
bent at an angle. Toward the head it tapers very slightly, and when 
alive a " pouting " movement as if of breathing can be seen at its very 
extremity. About the middle of the body a granular aggrpp:atinu 





\\\ 



V 



Fig. 36.— Tail of Filaria, slio\ying Prolongation of tbe Stieatb beyond the End i>t the Euibry.^ 
Itself. Magnified 800 diameters. 

can be made out along the central axis of the animal. Except for 
this granular portion the parasite is so translucent that it is not easy 
to make it out at first. The distinction of body and sheath men- 
tioned above appears as a " clear space " at each end of the body 
{vide Fig. 36). After the motions have ceased it becomes darker 
and traces of transverse striation may be seen (Fig. 38). 

It has no locomotive power and confines itself to wriggling in 
the same spot. Saussure ^ says he has watched them " fighting with 
each other for hours." 

2 Philadelphia Medical News, June 28th, 1890, where he reports twenty 
cases seen in Charleston. S. C. 



FILARIASIS. 



477 



The liead of the filaria is said by some authorities to be supplied 
with feelers or flagella, and Manson describes what he calls a " ceph- 
alic armature" or fang (Fig. 39). 

The same organism can sometimes be found in the chylous urine, 
but not every case of chyluria is due to the filaria sanguinis hominis. 
In a considerable portion of cases no such organism is to be found. 



Fig. 37.— The Movement of a Single Filaria during Four Successive Exposures of One-ilfth of a 
Second Each, the Entire Series Occupying less than Five Seconds. Magnified 800 diameters. 

Henry ' succeeded in staining the parasites i^itra vitam by giving 
the patient considerable doses of methylene blue internally for some 
weeks. Only a faint bluish tinge was imparted, however, to the 
organism by this method. 

For finding the parasite it is best to use a low power, not an im- 
mersion lens, and the whole of several slides should be looked over. 

Specimens can be dried and preserved for staining provided we 
do not heat them over a lamp or pass them through a flame. Fixa- 
tion in alcohol and ether and staining with thionin work well. 
]\Ianson ^ stains with eosin and mounts in " glycerin jelly." 

1 Med. News, May 2d, 1896. 

"-•'The Filaria Sanguinis Hominis," by Patrick Manson, M.D., Amoy, 
China, 1883. 



478 



SPECIAL PATHOLOGY OF THE BLOOD. 




Fig. 38. 



structure and beginning granular degenc 
] /M\ diameters. 




Fii.. 



ii'O. !..>>' l*uiiiierers. The blur iu frout of ilie head may be dut 
to the motion of flagella. 



FILARIASIS. 



479 



Several other species have been observed in England in negroes 



from the Congo River, bnt not hitherto in Amei 



'ica. 




Fig. 40.— Ilcud >,i rHaiid 



)l)ing a KiMi ( i,ipu>( le. Tin- apiuniiaiicf/ uiiglir br mistakeu for 
the cephalic end of a sheath. 



Considerable interest has lately been aroused in the morphology 
of the blood in filariasis : 









^ 


A 


•A 


■ 


f 














■^B 








i 


Red cells. 


White 
cells. 


S 

If 


if 
si 


55 >> 
If 


ill 

'^ 3j ^ 


If 


Remarks. 


a 






a 


a 






<D 




1 


4,876,000 




88 i 63.9 


23.1 


9 


3.4 


Da Costa. 


2 


4,200,000 


8,000 


88 ! 55.7 


34.2 


.6 


9.5 


Da Costa. 


3 




6,500 


.93 


56.6 


35.3 


3.6 


4.3 


Da Costa. 


4 


6,616,000 


8,000 


93 


55.8 


38.2 


1.4 


4.6 


Lotlirop and Pratt. 


5 








34 


44 


7 


15 


Coles.' 


6 








43 


33.8 


6.5 


17 


Coles. 


7 




6,800 




68.5 


24.5 


* 


7 


December 1st, 4 p.m. 






1,250 




55.5 


32.5 


* 


12 


December 11th, 11 p.m. 






4,600 




57.5 


36.5 


* 


6 


December 12tli, 10 a.m. 






13,100 




59 


31.5 


* 


9.5 


December 12tli, 11 p.m. 






5,000 




65 


32 


* 


3 


Januarv 31st, 10 a.m. 






6,300 




66 


29 


* 


4.5 


January 31st, 3 p.m. 






10,100 




61 


31 


7f 


8 


January 31st, 10 p.m. 






10,600 




67 


26 


* 


7 


February 8th, 10 p.m. 
Gulland.2 


8 








52.5 


40.5 


* 


7 


Gulland.-^ 


9 















7.5 


Yaquez.=^ 


10 






•• 


.... 






12 


Sicard.^ 



* Included with lymphocytes. 
' Coles: Brit. Med. Jour., May 10th, 1902. 

2 Gulland: Brit. Med. Jour., April 5th, 1902. 

3 Vaquez: La Sem. Med., December 17th, 1902. 



^Sicard: Ihidem. 



480 



SPECIAL PATHOLOGY OF THE BLOOD. 



In the preceding taljle L have arranged some of the briefer 
records. The best studied eases are those of Calvert' which are 
exhibited in the following taljle. 

Taiji.i-: CIX - Calveist. Case I. 









, 


A 


e 


X 












• 


£ 




S*^ 


e . 


t> 












S" *^ 


>-.-ki 




s*^ 








Date. 


Hour. 


t 


li 


Is 


^S£ 


it 


ft 


si 


= 






^ 


a t. 


e-t- 


^ C i 


5 - 




r 


- 








>>ai 


^- 


= c 


;= 2' 


•= o 












cO. 


^ 


£- 


o ^ 


— 


£ 






^ 


p: 


J 




C-i 


w 


b. 


- 


April 18th 


9 a.m. 


2:{,000 


60 


12 


4 


4 


20 





4,720.oorj 




10 A.M. 


]8,(K)(J 


65 


12 


4 


2 


17 









n A.M. 


IS.WKI 


a5 


9 


3 


3 


20 









12 m. 


1H..")()(» 


59 


11 


6 


3 


21 









1 P.M. 


26.WI0 


60 


10 


4.5 


2.5 


20 









2 I'.M. 


24,400 


58 


10 


5 


5 


'^ 









3 P.M. 


20,0!X) 


60 


11 


4 


4 


21 









4 P.M. 


18,600 


67 


12 


3 


3 


15 









O P.M. 


IH.OUO 


65 


11 


o 


3 


16 


u 






6 P.M. 


20,000 


m 


14 


o 


5 


13 


84 






7 P.M. 




61 


16 


5 


:y 


12.5 


252 






8 p.m. 




60 


14 


4 


3 


19 


3M 






9 P.M. 




68 


13 


5 


3 


11 


672 






10 P.M. 




6n 


13 


o 


•> 


15 


840 






11 P.M. 




m 


15 


4 


3 


15 


1,176 






12 M. 





67 


12 


5 


3 


8 


840 




April 19th 


1 A.M. 




65 


12 


4 


o 


17 


6r2 






2 a.m. 




64 


10 


3 


2 


21 


840 






3 a.m. 




69 


10 


3 


3 


15 


672 






4 A.M. 




71 


11 


3 


3 


11.5 


672 






5 A.M. 




64 


11 


4 


3 


18 


504 






6 A.M. 




65 


12 


4 


3 


15 


504 






7 a.m. 


18,600 


63 


13 


3 


3 


17.5 


84 






8 A.M. 


22,000 


6.5 


13 


4 


4 


14 









9 a.m. 


18,600 


64 


12 


4 


3 


16 


84 




April 27th.. , 


9 A.M. 
10 A.M. 


2:3,000 
18,000 


68 
60 


13 
16 


3 
4 


2 


18" 


84 
252 


5,300.000 


May 1st. 


5,200,000 


May 6th 


2 a.m. 
8 a.m. 


20,000 
17,000 


66 
66 


12 
13 


4 
4 


3 
3 


15 
14 






5,160,000 


May 8th 


5,200,000 







Table CX.— Calvekt. Case IL 











^ 


1 


1 




i. 




























a: 




.2 c 


5i = 


Large 

raononuc 

per cen 




■= r 




Date. 


Hour. 






B9 


-^ 




^t 








i; 


J 

S 

^ 


|i 


|l 




■fa 


£ 


April 18th 




3,600,000 


8,000 


64 


14 


4.5 


2.5 


15 




April 23(1 


2 P.M. 

3 p.m. 


3..5.50.000 


7,600 
8,000 


68 
70.5 


19 
15 


3.5 
3.5 


3 
3 


6.5 

8 


84 









4 p.m. 




8,000 


66 


19.5 


4.5 


2 


8 







5 p.m. 




6,600 


67 


20 


3 


2.5 


7.5 


Si 




6 p.m. 




13,000 


66 


20 


4 


3 


7 


84 




7 p.m. 






68 


20 


3 


9 


< 


504 




8 p.m. 






70 


16 


4 


3 


6.5 


588 




9 P.M. 






64.5 


23 




3 


6.5 


1.68U 




10 P.M. 






67 


18 


4 


4 


7 


1.596 




11 P.M. 






m.5 


22 


4 


2.5 


7 


l.ol2 




13 M. 






65 


21 


3 


2 


6 


1.428 



Calvert : Johns Hopkins Bull. , June, 190'^ 



SPIROCH^.TE OF RELAPSING FEVER. 

Table CX.— Calvert. Case II. {Continued) 



481 



Date. 


Hour. 


1 


1 
S 

s 


H 


1. 

|l 


IP 


11 




1 


April 24tli 


1 A.M. 
'Z A.M. 

3 A.M. 

4 A.M. 

5 A.M. 

6 A.M. 

7 A.M. 

8 A.M. 

9 a.m. 

10 A.M. 

11 A.M. 

12 M. 

1 P.M. 

2 p.m. 
2 p.m. 


3,289,666 
3,500,000 


'8,6(k) 

12,000 

10,600 

8.600 

7,000 

7,600 

8,000 

10,000 

8,000 

14,000 

12,000 


65 

&5 

67.5 

67.5 

61 

64.5 

60.5 

60 

60.5 

65 

64 

66 

68 

64 

52 

60 


22 

22 

22 

19 

18.5 

19 

32 

25 

15 

11 

16 

15 

14 

20 

26 

20 


3 

3 

3 

3.5 

4 

3 

3 

4 

2.5 

4.5 

4 

4 

4 

4 

6 

6 


2 
3 
1.5 

2 
.3 
2 
3 

1.5 
2 
2 

2 

2 

3 

2 


8 

3 

6 

8 

14.5 
10.5 
12.5 

8 

20.5 
12.5 
15 
15 
12 
11 
13 
12 


1,008 


May 6th 


1,008 

840 

612 

504 

168 

756 

1,092 

336 

588 

336 

84 



84 

336 


Mav 8th 










From these cases it appears that eosinophilia is a constant fea- 
ture of recently acquired cases and occurs to a less extent in chronic 
cases. It is usually most marked in the hours when filarise are 
fewest in the peripheral blood and decreases as the filarise increase. 

SPIROCH.ETE OF RELAPSING FEVER. 

During the febrile paroxysms of relapsing fever, and for one or 
two days before them, Obermeyer and others have found constantly 
present in the peripheral circulation a parasite whose length aver- 
ages about six times the diameter of a red corpuscle. Even under 
high-power lenses it is a mere thread in width, curled upon itself 
like a corkscrew and actively motile, so that in examining the blood 
with a low power we get a " peculiar impression of disturbance " 
among the red cells. 

The number of twists in this spiral-shaped organism varies a 
good deal, and one of its motions consists in contracting and extend- 
ing itself like a spiral spring. It can thus multiply its own length 
three or four times. It has also a delicate, wavy, but rapid motion 
along its long axis. The whole thread, or a part of it only, may 
have these motions. Further, the whole parasite has power of loco- 
motion apparently independent of the currents in the blood plasma 
of a slide and cover- glass specimen. Its locomotion is slow com- 
pared to the movements above described. Particularly in the blood 
post mortem they are apt to wind themselves into each other so as 
31 



482 SPECIAL PATHOLOGY OF THE BLOOD. 

to seem much larger than they actually are, and sometimes a large 
" nest " of them may look like a leucocyte, except for the fine wavy 
threads whicli can be seen in motion at the periphery of the mass. 




Fio. 41.— Spirochgetes of Relapsing Fever in Human Blood. 

The number present in the blood is very much smaller at the be- 
ginning of a paroxysm than after tlie second day. During the first 




Fig. 42.— Spirochsetes of Relapsing Fever in Human Blood. 

few hours of a febrile period Moc3mtkowsky could find only one 
spirochaete in ten or twenty microscopic fields, while later on he 



SPIROCHETE OF KELAPblNCi FEVEK. 483 



' v^ ^/^ ^ 




..J 


^O 




'-■ ""^■^-N. '*-. 




"\ 


•^"^ 


Oil' -^ - 




?t5v' 1 
'% o 1 


, ^~ ""x> 


"^ -, "-- 




FIG. 43. 






Vw^ 






FIG. 44.— Spirochaetes of Relapsing Fever. 



484 



SPECIAL PATHOLOGY OF THE BLOOD. 




y^^ 



saw twenty or thirty of them in a single Held. There are usually 

more parasites with each successive paroxysm. 

Blood taken from different parts of the body often shows a great 

difference in the number of organisms to be found. The life history 

of a single parasite seems to be very 
short, but they multiply with tliL^ 
greatest rapidit}'. Albrecht has seen 
them so increase within six hours th.at 
whereas at first he saw only a few in 
the whole slide he later found many 
in eacli field. As the spirochsete 
dies, its movements get languid, and 
finally it breaks up into small gran- 
ular bits (spores?). 

Between paroxysms the spiro- 
chaetes are not found, but there are 
to be seen peculiar highly refractile 
globules compared by v. Jaksch to a 
diplococcus. The latter author lie- 
lie ves that he has seen these develop 
into the spirochaete at the beginning 
of a paroxysm and hence believes 
them to be spores. 

This spirochaete is found in all 
cases of relapsing fever and in no 
other known disease, so that like the 
Plasmodium malariae it is pathogno- 
monic and of the highest importance. 
Anaemia and leucocytosis (during 
the paroxjTm) are among the sec- 
ondary results of the presence of this 
parasite in the blood. 

Boeckmau reported that the red 
cells sink during, and for one to two 
days after, the attack, increasing 




Fig. 45. 



-Leucocytes Containing 
Spiroctii:etes. 



somewhat in the afebrile periods. 
Laptschinsky, Heidenreich, and 
Boeckmami all noted considerable leucocytosis. Laptschinsky 
mentioned the presence of a very large number of coarsely granular 
leucocytes. 






SPOTTED FEVER OF THE ROCKY MOUNTAINS. 485 

A certain resemblance has been noted between the spirochsete 
and a free flagelhim broken off from a malarial parasite, bnt the 
clinical history and the presence or absence of other evidence of 
malaria in the blood would easily decide the question of diagnosis. 

Technique of Examination. — As in looking for the malarial or- 
ganism, it is best to examine the blood fresh between a slide and 
cover-glass {vide page 7) and to use an oil-immersion lens. In 
dried specimens the organism can be stained with fuchsin, but 
it is much more difficult to recognize than in the fresh blood. The 
spirilla stain well with aniline dyes, and Karlinski succeeded in 
demonstrating flagella with some individuals. Concentrated solu- 
tion of methylene blue stains all spirilla in from two to five minutes. 
Phagocytosis (see Fig. 45) can easily be watched in the peripheral 
blood. 

SPOTTED FEVER (TICK FEVER) OF THE ROCKY MOUNTAINS. 

The parasite of this newly described disease was first discovered 
by Drs. L. B. Wilson and W. IsV. Chowning ^ of the University of 
^linnesota, whose services were engaged in the spring of 1902, by 
the Montana State Board of Health, to investigate an epidemic then 
prevailing in the Bitter Root Valley. Their report was published 
July 19th, 1902. Their findings were confirmed by Surgeon J. 0. 
Cobb,^ by Prof. F. F. Wesbrook,^ of the University of Minnesota^ 
and by Passed Assistant Surgeon John F. Anderson * of the United 
States Hygienic Laboratory at Washington. Altogether seventeen 
cases have been examined with positive findings in all. The para- 
site most resembles that of Texas cattle fever as described by Theo- 
bald Smith (^pyrosoma bigemiicm). 

It is found chiefly in the red cells but occasionally outside; is 
non-pigmented and shows amoeboid movements. Three forms are 
described: ''The most common is a single ovoid body, highly re- 
fractile and usually situated iiear the edge of the cell." While the 
slide is warm the parasite projects pseudopodia rapidly and slightly 
changes its position. It is 1.5 to 2 ,a long and half as wide and 

1 Wilson and Cbowning : Report of 3Iontana Board of Health, 1901-02 ; 
Joum. American Med. Assn., July 19tli, 1902. 

•2 Cobb: Pubhc Health Reports, August loth, 1902. 

3 Wesbrook: Report of Minnesota Board of Health, 1901-02. 

■i Anderson. Hygienic Laboratory, Bulletin No. 14, July, 1903 (Washing- 
ton, D. C). 



486 



SPECIAL PATHOLOGY OF THE BOLOD. 



Tesembles the youngest parasite of aestivo-autuinnal iiialaiia. 
'"Another form, less common, is larger, especially at one end where 
a dark granular spot appears." A third form, distinctly pyriform, 
is arranged in pairs, with the smaller ends approaching and some- 
times joined by a minute thread. In this no motion is seen. 

The parasite is best stained by some method giving the Ronifi- 
■nowsky stain. It stains blue against the pink of the red corpuscles, 
but it is always difficult to bring it out clearly. The parasite takes 
the stain more deeply at one end. Sometimes it has a central 
.stained spot surrounded by a clear unstained space. 

In specimens stained by some one of the Romanowsky stains 
(Nocht's, .Tenner's, Wright's) the parasite sometimes shows a red 
or violet chromatin body, while the rest of the body stains blue 
against the pink of the corpuscles. It is usually necessary to searcli 
several fields before finding a parasite, but rarely as many as eleven 
occur on a single field. Aside from the presence of these parasites 
the blood shoAvs only an anaemia. Throughout the course of the 
disease there is " a steady but never very rapid decrease in the per- 
centage of haemoglobin, one case going as low as fifty per cent." The 
erythrocytes are sometimes moderately diminished. The leucocytes 
are not increased or diminished. In the two differential counts on 
record thus far a slight increase in the large mononuclear forms Avas 
noticed. 

DISTOMUxAI HAEMATOBIUM (BILHARZIA DISEASE). 

Eosinophilia lias recently been reported. The following figures 
exemplif}' it : 



Hed cells. 


White 

ceUs. 


Per cent 
hsemo- 
globln. 


Per cent 

poly- 
nuclears. 


Per cent, 
small lym- 
phocytes. 


Per cent 
large 
mono- 
nuclears. 


Per cent 
eosino- 
phlles. 


Reported by 


4,650,000 


8,200 


84 : 49 
46 


21 

27 


18 

7 


12 

20 


Manson. ^ 
Coles. '^ 



Douglas and Hardy (Lancet, October 10th, 1903) studied 50 
cases, and found leucocytosis and an eosinophilia averaging 16.5 
per cent; 21 cases showed over 15 per cent of eosinophiles, and 
but 2 were below 6 per cent. Despite the absence of malaria the 
large mononuclears averaged 12.5 per cent, 10 being above 15 per 
cent. 

1 Manson: Brit. Med. Jour., December 20th, 1902. 

2 Coles: IMdenu Mav lOtli. 1902. 



TRYPANOSOMIASIS. 



487 



FRAMBGESIA. 

Glogner ^ in eight cases found an increase of lymphocytes, slight 
or marked. 

TRYPANOSOMIASIS. 

The first discovery of a trypanosoma in human blood was made 
in Gambia, in 1901, by Dutton,^ of Liverpool, who found it in two 
persons, one a child without symptoms, the other an adult English- 
man with chronic fever, wasting, splenic enlargement, and circum- 
scribed, fugitive oedema. Laveran, referring to these cases, dubs the 




Fig. 46. -Trypanosoma In Human Blood. (By permission of Dr. J. Everett Dutton and the 

London Lancet.) 

parasite Trypanosoma Gambiensis,' and states that it is conveyed 
to man as to other animals by the fly Glossina palpalis. 

An expedition sent to Gambia in 1902 by the Liverpool School 
of Tropical Medicine' found 5 cases among 221 examined; the 
number of parasites was from 1 to 23 per cover slip (see Fig. 46). 

These observations have been confirmed by Forde,' Daniels," 

1 Glogner: Virchow's Arch., vol. 168. 

2 Dutton: Brit. Med. Jour., September 20th, 1903. 

3 Laveran: Bull, de lAcad. de Med., May 27th, 1902. 
* Referred to in Brit. Med. Jour., February 7th, 1903. 
sForde: Jour, of Tropical Med., September, 1902. 
^Daniels: Ibidem, November, 1902. 



488 SPECIAL PATHOLOGY OF THE BLOOD. 

Maxwell Adams,' Manson,* Leishman,-' Baker* (three cases), and 
others- Some anaemia results in chronic cases. About twelve cases 
in all are now on record. 

Manson " describes the human trypanosome as seen in the fresh 
blood as " a minute, colorless, transparent and very active vermicule 
tapering toward its extremities, one of which ends in a long flagel- 
lum continuous with the undulating membrane attached to nearly 
the entire length of one side of the body." Xear the end opposite 
that bearing the flagellum is " a refringent speck — the centrosome. 
The organism is always free in the plasma, never intracorpuscular. " 

Stained by any of the Komanowsky stains (e.^., Wright's) the 
body of the parasite is blue, the flagellum and the free edge of the 
undulating membrane are pink, the centrosome is deep red, wliile a 
nucleus, also pink staining, appears about the centre of the body. 

The length of the parasite is from two to three times that of a 
red cell; its width about one-fourth of that of a red cell. When in 
activity it rotates with a screw- like motion upon its long axis. The 
number of parasites found in the cases thus far observed has 
been scanty — three to eight in a three-fourth inch cover-slip prep- 
aration. 

This trypanosome has also been found by Castellani, Bruce, and 
others, in the blood and cerebro-spinal fluid of cases of sleej^ing- 
sickness, and is believed by ^lanson to be the cause of this disease. 

ANEMIA DUE TO INTESTINAL PARASITES. 

The bothriocephalus latus, uncinaria duodenale, and a few other 
parasites are capable of producing by their presence in the in- 
testine a very severe anaemia, which may be indistinguishable from 
pernicious anaemia. Bothriocephalus anaemia has been studied by 
Schaumann in a monograph (Berlin, 1894, Hirschwald) which is the 
very acme of careful, conscientious work and eclipses entirely the 
fragmentary observations of earlier writers. Uncinariasis has been 
thoroughly studied by B. K. Ashford of the United States army in 
Porto Eico, by Boycott and Haldane,' Sand with, and others.' 

' Maxwell and Adams. Brit. Med. Jour., :March 28th, 1903. 

2 Manson: Brit. Med. Jour., May 30tli. 1903. 

3 Leishman: Brit. Med. Jour., May 30th, 1903. 

^ Baker : Ibidem. ^ Manson : " Tropical Diseases, " 1903. 

^ Boycott and Haldane; Journ. of Hygiene, Jan , 1903. '' See p. 490. 



( 



BOTHRIOCEPHALUS ANEMIA. 489 

BOTHRIOCEPHALUS ANEMIA. 

The presence of the bothriocephalus latus in the intestine of 
man is usually accompanied by anaemia. In certain cases, however, 
under conditions not at all clear at present, there is produced an 
anaemia of the severest type, differing from ordinary pernicious 
anaemia only in its curability through the expulsion of the worm. 

Schaumann's magnificent study of the blood of thirty-eight cases 
resulted in the following data : 

1. Eed cells at time of first examination : 

2,000,000 to 2,500,000 in 1 case (2,150,000). 
1,500,000 " 2,000,000 " 9 cases. 
1,000,000 " 1,500,000 " 17 " 
500,000 " 1,000,000 " 10 " 

Uuder 500,000 " 1 case (395,000). 

38 cases 
Average of all, 1,290,000. 

2. HcBmoglohin (first test) : 

30 to 40 per cent in 7 cases. 
20 " 30 " " 18 " 
10 " 20 " " 13 " 

38 cases 
Average, 25 per cent. 

3. Color i7idex : Less than 1 in 8 cases (0.9 to 0.99), more than 
1 in 30 cases. Average, 1.09. 

4. Average diameter of red cells, 7.4 /^ (slightly above normal). 

5. Poikilocytosis marked, but its degree is not parallel with the 
degree of anaemia. 

6. Eouleaux formation always defective or altogether absent. 

7. Poly chromatoph ilia and stippled red cells are common. 

8. Nucleated red cells present in all cases examined for them — - 
2Q — but without parallelism with the degree of anaemia. 

Megaloblasts predominated in over half the cases. In 5 cases 
megaloblasts only appeared; in one case normoblasts only. In the 
other 20 cases both types were present. Mitoses were found in 2 
cases. 

Leucocytes were usually normal or subnormal in number. 

Differential count practically as in pernicious anaemia. 

The eosinophiles are noted as " very scanty " in 25 cases and 
" apparently somewhat increased " in one case. [This is in sharp con- 



490 



SPECIAL PATHOLOGY OF THE BLOOD. 



trast with the eosinophilia usually present in ankylostomiasis {cklt^ 
page 116.)] A few myelocytes were noted in two cases with leuco- 
cytosis 

Blood platas diminished. 

So far the figures refer to untreated cases at the worst stage of 
the disease. Five-sixths of the cases were entirely and apparently 
permanently cured in about two months by the' expulsion of the 
worms. Blood counts at the time of leaving the hospital showed : 

In 3 cases about 2,500,000 red cells 
" 2 " " 8,000,000 " 
" 2 *' " 3,500,000 " 

" 16 '•' " 4,000,000 " 
" 4 " " 4,500.000 " 
" 4 " " 5,000,000 " 

Average 4,680,000 (10 cases still higher) with 70 per cent haemoglobin. 

Thirteen of these were followed up after discharge, and in these a 
full restitutio ad integrum occurred. 

UNCINARIASIS (ANKYLOSTOMIASIS). 

The first careful observations of the blood of which I have 
knowledge are those of Zappert in 1892,' wlio reported a moderate 
grade of anaemia with low color index. 

^liiller and Kieder - were the first to note the eosinophilia which 
later observations have shown to be so frequent. They record 8.2 
per cent and 9 7 per cent in two cases of the disease. Zappert refers 
to two cases with 17 per cent of eosinophil es. 

Rogers ^ compares the ansemia produced b}^ the uncinaria with 
that due to malaria and with the blood of the average native of As- 
sam, where his studies were carried on His results are shown in 
the following table : 



Healthy Assamese 
Chronic malaria. . . 
Ankvlostomiasis. . 



Red cells. 



4,734,000 
2.000.000 
1,145.000 



White cells. 



7,325 
1,600 
5.388 



Haemoglobin. 



67 per cent. 

31 

15 



Rogers does not refer to the percentage of eosinophiles. 

I Zappert: Wien. kliu. Woch., 1892, No. 24. 
^Muller und Rieder: Arch. f. kiln. Med., vol. xlviii. 
sBrit. Med. Journal, 1900, p. 539. 



UXCINARIASIS (ankylostomiasis). 
In 1894 Bucklers ' reported the following counts 



491 





Case I. 


II. 


III. 


IV. 


y. 


yi. 


Red cells 


3,649.000 
13.000 

46 
37 


15,666 

"4%' 

74 
22 


3,954,000 
20.600 
45.0,^ 
53.6 
22.3 
25.1 


10'.4,'i 

46 

43.6 


21^ 
22 
53 
25 




White cells. 




Haemoglobin 


'>r» 0^ 


Eosinophiles 


9\ 


Polyniiclear 


30 


Lymphocytes and transi- 
tionals 


46.6 



Leichtenstern (referred to by Ehrlich and Lazarus) illustrated 
the behavior of the eosinophiles in the presence of a secondaiy in- 
fection b}^ this case : ''In the blood of a very anaemic , almost mori- 
bund patient with ankylostomiasis there were found, in 1897, 72 
per cent of eosinophiles. The patient contracted a croupous pneu- 
monia, and in the high febrile period of the disease the eosinophiles 
sank to 6 and 7 per cent, rising again after the termination of the 
pneumonia to 54 per cent , After removal of the worms the eosino- 
philes fell at once to 11 per cent. 

'• In 1898, when the faeces contained but very few ankylosto- 
mata, . . . the eosinophiles amounted to 8 per cent.'' 

The Blood ix Gross. 

The best studies of the disease are those of Ashf ord ^ and of 
Boycott and Haldane. ^ The latter studied an epidemic observed in 
Cornwall miners. They found the total volume of blood (Haldane 's 
method — see above, page 6) increased as in chlorosis and very 
different in this respect from the conditions found in pernicious 
anaemia. Indeed they insist that the blood of uncinariasis rarely 
simulates to any extent that of pernicious anaemia. 

lied Cells and Hcemoglobin 

Their counts varied from 1,500,000 to 5,400,000 in 33 cases. 
The color index was loiv in all but 4 cases, — the lowest figures being 
0.53 and the highest 1.38 (17 per cent to 104 per cent). In general 
the more profound the anaemia, the less the tendency to a high color 
index such as is the rule in pernicious anaemia. 

In most of their cases the loss of red cells was not extreme; 

1 Bucklers: Munch, med. Woch., 1894, No. 2. 

2 Ashf ord: Amer. Med., 1908, p. 391. 

3 Boycott and Haldane: Jour, of Hygiene, 1903, vol. iii.. No. 1. 



492 SPECIAL PATHOLOGY OF THE BLOOD. 

poikilocytosis was present in but few cases and never extreme; a 
few showed variations in size Ijeyond the normal. In one case fwith 
1,500,000 red cells) the cells showed polychromasia with live normo- 
blasts, two questionable megaloblasts, and abundant megalocytes; 
two other cases showed one or two normoblasts. 

This epidemic was a comparatively mild one, which probably 
accounts for the difference bt^tween these blood changes and those 
reports by Ashford, among which 16 out of 50 showed less than 
2,000,000 red cells per cubic inillimetre. Of a former series of 19 
cases,' 11 fell below 1,000,000, 14 had normoblasts, and 6 of them 
showed megaloblasts. In Ashford" s series, as in that of Boycott 
and Haldaue, megaloblasts never predominated. Poikilocytosis 
was present in all Ashford's cases. In Capps' ' case the count sank 
in two months from 2,576,000 to 748,000; the haemoglobin was al- 
ways relatively low (color index 0.38 to 0.88) with scanty normo- 
blasts and no megaloblasts. At autoj^sy the marrow was yclhur^ 
i.e., showed no compensatory regeneration. 

In the case reported by Evans, ^ the red cells averaged 2,500,000, 
in Yates' "' case they sank within a week from 2,500,000 to 800,000. 

In Ashford's second series ^ of 77 cases, 130 examinations were 
made (excluding those when only the haemoglobin was tested). 
The color index was alwa3's low, but the count of red cells fell only 
twice below 1,000,000. 

Sand with '^ studied in Egypt 173 cases. Of these only 3 ex- 
ceeded 4,000,000 red cells per cubic millimetre; 23 per cent were 
found to have between 3,000,000 and 4,000,000; 46.8 per cent lay 
between 2,000,000 and 3,000,000, and 28.3 per cent had less than 
2,000,000. His minimum count was 930,000, and his average 
count of hospital cases was 1,290,000 per cubic millimetre. The 
average of all cases is 2,420,000; the haemoglobin, 26 per cent; the 
average color index 0.54 per cent. 

In many of the recorded cases the abrupt rise and fall in the 
red cells is astonishing. 

In view of all the evidence it appears that the contradictions be- 

1 Ashford; New York Med. Jom\, 1900, p. 552. 

2 Capps : Jour. Am. Med. Assn., January 3d, 1903. 

3 Evans: Ibidem, April lltb, 1903. 

"^Yates: Johns Hopkins Bull., December, 1901. 

5 Ashford; Amer. Med., 1903, p. 391. 

^ Sand with; Eleventh Internat. Med. Cong., Rome, 1894. 



UNCINARIASIS (ANKYLOSTOMIASIS). 493 

tween the statements of such writers as Boycott and Haldane, who 
assert that the blood resembles chlorosis, and the reports of many 
other writers that it resembles pernicious anaemia, depend in part 
upon the great variations in the severity of different epidemics. In 
the milder cases or in the earlier stages of any case we get counts 
like those of chlorosis or any other secondary ansemia of moderate 
grade. In severe cases, however, the count may fall as low as in 
average cases of pernicious anaemia. The volume index (Capps), 
determined by comparing the length of the packed-down column in 
the hsematocrit with the count of red cells, may be high, as in per- 
nicious anaemia (1.17 to 1.22 in Capps' case); but the coloi' index is 
low in practically all the recorded cases, whether mild or severe 
(Ashford, 0.51 in 61 cases, Sandwith 0.54). 

Leiicocytes. 
In Boycott and Haldane's series the range was from 3,800 to 
56,000; but in 16 of the severer (anaemic) cases the average was 
13,600. They found that the maximum leucocytosis occurred early 
in the disease before the anaemia was severe. The highest counts 
(56,000, 44,000, 24,000, and 20,000) were all in young men with a 
history of from six weeks to six months' illness and with relatively 
slight symptoms. The lowest counts (3,800, 6,200, 6,700, and 
6,800) were in cases of from two to four years' standing. In all but 
one of Ashford' s cases (presumably more chronic), the leucocytes 
were normal or subnormal. 

Differential Count. 
The main feature, agreed upon by all observers, is the marked 
eosinophilia, absolute and relative. According to Boycott and Hal- 
dane the eosinophilia varies with the total leucocyte count, that it 
is highest in fresh, early cases occurring in young men, and less 
marked in the long-standing cases. It bears no close or direct rela- 
tion to the degree of anaemia. The averages in sixteen anaemic cases 
were : 

Eosinopbiles 33 per cent or 8,059 absolutely 

Polynuclears 48.7 " " 6,477 

Small lymphocytes 14.4 " " 1,91,5 " 

Large mononuclears 5.9 " " 785 " 

Intermediate forms 7 4 " " 984 " 

Mast cells 6 " " 80 

In one case the mast cells were 2 5 per cent, but in 6 out of 58 
cases none was found. 



494 



SPECIAL PATHOLOGY OF THE BLOOD. 



The detailed results of this admirable study are exhibited in the 
tables on page 494. 



lOct 
Nov 
Dec. 
Oct. 
Nov 

3 

4 Oct. 
Nov 
Nov 



10 



12 



Nov. 
Nov. 
Nov. 
Dec. 
Dec. 
Dec. 
Nov. 
Nov. 



Dec. 12 
Dec. 19 



3 years. 



4 years.. 



4 years. 
4 years. 



5 years. . . 
3 years... 
2 years . . . 

6 years . . . 
2 months. 



1 year. 



18 months. 



(3,192,000 



4 years . . . 
8 months. 

8 years... 

4 years... 
3 years... 
2 years. . . 

1 year — 

2 years. .. 

3 years . . . 
6 years... 

9 months. 
9 months. 

5 years. . . 

5 weeks . . 

6 months . 
8 years . . . 

5 years. .• 
few weeks. 

2 years. . . 
lyear — 

1 year — 

6 years. .. 

2 years. .. 

2 years. . . 
18 months. 

3 years... 



6 years. 
2 years . 



8 years . . , 
5 months, 



3,216,000 



2,192,000 



3,024,000 
3,328,000 



3,968,000 
3,376,0(J(J 
4,424,000 
4,712,000 
4,936,000 
3,432,000 



1,53:3,000 
2,192,000 



.3,768.000 
3,3:30,000 
4,072,000 
4,488,000 
4,128,000 
3,352,000 
3,456,000 
5,384,000 
5,280,000 
3,272,000 
4,848,000 
3,144,000 
3,216,000 
4,080,000 
3,296,000 
5,112,000 
4,208,000 
4,176,000 
4,706,000 
5.350,000 
2,900.000 



50 



100 



0.74 



.81 



.71 

.79 

.83 

1.00 

1.04 



.63 

l.:38 

.71 

1.11 

90 

53 

1.01 

58 

66 

1.37 

.91 

.74 

72 

!98 

.67 

.98 

1.16 

l.TO 

.70 



8,800 



3,800 



6,8()0 
8,200 



7,500 
1:5, 1(K) 
10,750 
12,700 
1{|,(KXJ 
24,400 
31,400 
12,960 
12,200 
7,690 
7,850 
44,000 



16.200 

13..500 

13..500 

6,200 

12.400 

10.700 

9,2.50 

9.000 

8,a50 

7,600 

8,100 

12,:300 

12,000 

11,100 

11,600 

6,900 

20,600 

13,600 

10,.500 

56.000 

6.700 

7.200 



14.2 
7.4 
18.4 
11.0 
6.3 
8.9 
9.0 
16.8 
20.6 
9.2 
36.6 
27.6 
17.5 
2.5.0 
37.8 
19.5 
31.0 
33.0 
10.6 
13.2 
20.2 
19.0 
23.8 
21.0 
14.8 
14.2 
5.4 
27.0 
12.8 
15.6 
21.6 
41.2 
15.6 
19.0 
14.2 
15.6 
15.6 
12.8 
13.6 
27.0 
8.0 
20.0 



tc 


y- 






a 




^ 













t-l 


3 




1 


C 


1 


"O 





i 




c 











fe 


1 


a 




es 










•"■ 




"^ 


7.4 


6.2 


56.2 


5.6 


3.4 


61.0 


8.2 


5.8 


51.0 


4.4 


2.2 


72.0 


11.0 


10.4 


50.0 


5.2 


5.2 


53.0 


3.0 


1.5 


39.5 


11.8 


7.8 


47.0 


13.4 


15.6 


4:3.0 


6.2 


7.0 


.54.4 


9.6 


5.9 


36.0 


4.0 


3.6 


55.2 


7.6 


4.2 


48.4 


2.4 


3.6 


62.8 


2.6 


3.2 


74.4 




5.2 


58.0 


i.8 


5.2 


67.0 


0.5 0.7 


19.5 


3,6 


0.5 


20.7 


3.1 


0.5 


20.7 


3.6 


3.0 


61.6 


3.4 


1.6 


45.8 


8.0 


8.0 


52.0 


6.6 


3.2 


40.2 


IS.O 


6.6 


4:3.6 


6.5 


2 8 


42.5 


6.4 


4.4 


.53.0 


7,4 


2.8 


38.6 


15,8 


6.8 


37.3 


3.8 


2.8 


48.2 


4.2 


3.8 


47.6 


9.0 


5.4 


42.8 


4,8 


4.6 


57.6 


4.2 


6.8 


55.6 


4.2 


3.8 


55.6 


4,4 


3.8 


47.0 


4.2 


1.2 


16.6 


7.0 


8.6 


51 8 


5.5 


4.0 


60.25 


5 4 


2,8 


25.6 


15,0 


7.0 


36.5 


11.2 


4.0 


52.0 


6.4 


3.4 


47.4 


3.0 


1.4 


69.8 


4.6 


2.4 


34.2 


3.0 


1.4 


55.6 


5.2 


1.6 


54.0 


5.2 


1.8 


69.0 


4,0 


5.2 


58.0 


6.4 


3.0 


58.4 


7.6 


8.8 


64.8 


10.2 


5.8 


62.4 


9.0 


1.8 


48.0 


7.0 4.75 


67.2.5 


20.0 


5.5 


61.0 



16.0 0.8 
18.0 1.2 



17.8 
8.8 
11.4 
19.4 

33.5 

16.8 
20.6 

6.0 
17.2 

5.6 
29.0 

15.8 
11.0 
17.0 
13.6 

6.5!8 
66.2 
14.6 
27.6 
22.0 
12.0 

3.7 
30.1 
10.4 
12.2 
20.6 
13.8 
11.2 
32.0 
19.0 
12.6 
16.6 
20.4 
56.2 
22.6 
15.25 
66.2 
14.0 
20.0 
26.4 

3.6 
17.0 
24.4 
20.2 

9.4 
16.4 
15.6 
10.2 

7.0 
13.8 
11.5 
13.0 



1.4 



11 
:2 



Normal 

240 



UNCINARIASIS (ANKYLOSTOMIASIS). 



495 



Regarding the eosinophiles, Asliford's conclusions from 77 cases 
studied in Porto Rico agree in the main with those of Boycott and 
Haldane: i.e., he finds the highest percentages in recent cases and 
the lowest in chronic cases. "After treatment in chronic cases and 
in those in the later stages of the disease a rise in eosinophiles may 
be expected and is of good prognostic import. When, however, 
there is a fall in eosinophiles and no improvement in physical signs, 
death may often be the result." Four out of five cases that died 
from the anaemia had relatively low counts of eosinophiles. After 
the patient is cured there is a final return to the normal percentage 
within from three to six months. 

Table CXI. — Schedule op Blood Examinations in Nineteen Cases at 
Ponce, Porto Rico, by Ashford. 



Date. 


1 
1 

1 


Red cells. 


4 
11 


White 
cells. 


>> 

^o o 

III 


I 

If 


fcco 

§1 


1 

o-g. 

II 


ii 

fl2 


■3S 


Remarks. 




e 




H 




sa 


2 


g 


s 


S ^ 


^g 






3 




V 




(V 


OP 




<a 


o « 








1 




(U 




CL, 


Ph 


Ph 


P-i 


S5 


^ 




Nov. 4th.. 


1,530,116 


lo" 


6,800 


65 


'2r 


9 


5 


26 


T3~ 


Poikilocytosls, Polychro- 


Nov. 23d.. 




1,880,000 


16 
















matophilia, many mlcro- 
cytes and maciocytes. 


Nov. 3d . . 


2 


697,776 


20 


7,960 


59 


17 


15 


9 


144 


46 


Poikilocytosls. Polychro- 


Nov. 23d.. 




2,664,440 


23 
















matophilia, many macro- 
cytes and mlcrocytes. 


Nov. 4th. . 


3 


1,533,112 


22 


2,000 


64 


22 


8 


6 


8 




Poikilocytosls. No rou- 


Nov. 23d.. 




1,973,328 


23 
















leaux. 


Nov. 5th.. 


4 


1,200,000 


15 


4,200 


64 


23.4 


6 


6.6 


109 


8 


Poikilocytosls. Polychro- 


Nov. 23d.. 




801,104 


17 
















matophllla. 


Nov. 6th.. 


5 


1,484,440 


10 


6,000 


64 


24 


8 


4 


12 




Poikilocytosls. Slight ten- 


Nov. 33d.. 




687,776 


14 
















dency to rouleaux forma- 
tion ; macrocytes and 
microcytes, latter pre- 
dominate over former. 


Nov. 6th.. 


" 


2,193,328 


23 


8,800 


65 


26 


8 


m 


123 


35 


Poikilocytosls. No ten- 
dency to rouleaux for- 
mation. 


Nov. 7th.. 


7 


1,633,328 


17 


5,600 


60 


23 


5 


12 


11 




Poikilocytosls. Many ma- 
crocytes and microcytes ; 
slight rouleaux forma- 
tion ; marked chromato- 
philia. 

Poikilocytosls. Rouleaux 


Nov. 7th.. 


8 


2,064,664 


23 


4,800 


74 


17 


6 


3 


28 




Nov. 23d. . 




3,084,440 


31 
















formation good. 


Nov. 7th. . 


9 


1,271,104 


14 


7,800 


60 


17 


6 


17 


30 


15 


Has elephantiasis Arabum, 


Nov. 23d.. 




2,520,000 


24 
















but I cannot identify 
the filaria as yet. Micro- 
cytes predominate over 
macrocytes. Good rou- 
leaux formation. 


Nov. 7th.. 


10 


1,600,000 


17 


1,500 


72 


20 


4 


4 


6 




Potkilocytosis. 


Nov. 23d. . 




668,888 


13 


















Nov. 8th.. 


11 


1,800,000 


25 


4,600 


69 


22 


'^ 


2 


9 




Poikilocytosls. 


Nov. 8th. . 


12 


2,296,656 


30 


7,680 


52 


26 


12 


10 








Nov. 9th.. 


13 


1,268,888 


20 


6,800 


63 


17 


7 


13 






Poikilocytosls. Rouleaux 
formation good. 


Nov. 9th.. 


14 


2,440,000 


25 


11,000 


50 


10 


9 


31 






Poikilocytosls. Rouleaux 
formation slight ; has 
abscess of liver. 



496 



SPECIAL PATHOLOGY OF THE BLOOD. 



Table CXI. — Schedule op Blood Examinations in Nineteen Cases at 
Ponce, Porto Rico, by Ashford {Continued). 









^ 






1 i 


/ 


. P 


^1 




Date. 


2 


Red cells. 


If 


White 
cells. 


^5 .S o 


Hi! 


2'i 




^2 


Remarks. 




CL, 




1,— 




Siri 


o "- ri 




= •- 


-z-~ 






C 




p 




£i2 


c: 


C 


s: 


i^ ci 


tl'2 










V 




0) 


0) 


a; 


K 










C 
1.5 








Ph 


0- 


tt- 


&. 


:^ 


,^ 




Nov.Qth.. 


2,a53,328 


17 


12,700 


73 


17 


4 


6 






Poikilocytosls. R(*uleaux . 


Nov.Qtb.. 


16 


2,934,444 




5,200 


72 


30 


5 


3 


10 


10 


Tertian malarial parasites 
found. Rouleaux grood. 


Nov. 10th. 


17 


2,140,000 


23^4 


18,000 


40 


12 


8 


40 


36 




Poikilocytosis. Rouleaux 
good. I believe this inaii 
to have been sufferintr 
from pneumonia at tiiin' 
of examination. 


Nov. 12th. 


18 


Unknown. 


:«) 


9,000 


60 


16 


10 


10 


125 




Poikilocytosis. Rouleaux 
formation good. 


Nov. 20th. 


19 


1,560,000 


16 


2,400 


72 


10 


o 


13 









Tliese two tables, the first from a relatively mild and recent 
epidemic, the second from a locality where the disease has probably 
been endemic for years, should give, I think, a fair idea of the range 
of variation in different groups of cases. 

The number of cases recently reported in this country is large. 
They are well summarized in Capps' article (loc. cit.) and in Stiles' 
monograph. ' 

Diagyiostir Value. 

The presence of eosinophilia in any case of anaemia should hence- 
forth suggest the examination of the stools for uncinaria eggs. 
There are other parasites which produce anaemia with eosinophilia 
{e.g., hydatids), but none is so common as the uncinaria, and since the 
discovery by Stiles that considerable regions of our Southern States 
are infested with an American species of the worm and that a form 
of anaemia produced by it is common among the " poor whites " of 
these regions, the practical importance of blood examinations has 
been increased. 



Effects of Treatment. 

Of Sandwith's 173 cases he states that the least gain on treat- 
ment was 310,000 red cells per cubic millimetre. Another case, 

^ Stiles: " Report on the Prevalence and Distribution of Uncinariasis in the 
United States." Hygienic Laboratory, Bulletin No. 10, February, 1903. 



TRICHINIASIS. 



497 



that of a boy, gained in one month seven pounds in weight and 
2,208,000 red cells per cubic millimetre. Ten patients gained over 
2,000,000, one of them 2,542,000. His average gain of all cases 
in haemoglobin was from 22 to 32 per cent. 

Agnoli' reports a case in which there was a gain of 2,168,000 
red cells per cubic millimetre and of twenty-six pounds in weight 
in thirty-five days. Eighty-five of Ashford's one hundred cases 
completely recovered. 

TRICHmiASIS. 

In March, 1896, a case of trichiniasis entered Professor Osier's 
wards at the Johns Hopkins Hospital. The study of the blood of 
this case by Thomas R. Brown was the means of calling the atten- 
tion of the profession for the first time to the value of blood exam- 
ination in the diagnosis of trichiniasis. The blood was examined 
daily for over two months. The total leucocyte count gradually 
rose from 17,000 at entrance to 35,700 forty-four days later. 
Thence it declined until, on the sixty-eighth day, it was 11,000. 
The eosinophiles were 37 per cent (6,300 absolute) at entrance, and 
rose with the total count until a percentage of 54 (19,500 absolute) 
was reached on the forty-fourth day (when the total leucocytes 
were 35,700). The highest percentage (68.2) was reached on the 
forty-ninth day, when the leucocytes were 17,700 (eosinophiles 
11,070 absolute). On the sixty-eighth day (the date of discharge) 
the eosinophiles were 68 per cent (1,850 absolute). 

A year later Brown studied a second case. His examinations 
showed as before a very marked eosinophilia (see table CXII.). 

Table CXH.— Case II.— Blood Chart. 



Date. 


Leuco- 
cytes. 


Percentage of the Various 

FORMS OF leucocytes. 


total Number of Various 
FORMS per c.mm. 




P.N. 

Neut. 


L. M. 

and T. 


s. 

Monos. 


Eos. 


P. N. 
Neut. 


s. 

Monos. 


L. M. 
andT. 


Eos. 


April 15th.. 
16th.. 


13,000 


43.1 

47.7 


6.5 

4.7 


1.4 
4.5 


42.8 
39.1 


5,600 


180 


840 


5,560 


17th.. 




52.0 


2.8 


7.6 


37.6 










18th.. 
19th.. 
20th.. 


8,000 
8,966 


57.2 
55.2 


2 8 
3.8 


8.0 
11.2 


32.0 

31.8 


4,900 


1,000 


340 


2,830 



1 Agnoli : " Consideraciones sobre dos cases cle anemia por Aukylostoma 
duodenal." La Cronica Medica, Lima, Peru, 1893, vol. x., p. 6. 
32 



498 SPECIAL PATHOLOGY OF THE BLOOD. 

Table CXIL— Case II. — Blocjd Chajit {Continued). 







Percentage of the Various 


Total NTmber of Various 


Date. 


Leuco- 
cytes. 


Forms of Leicocytes. 




fOKM.S PER C.M.M 






P.N. 

Neut. 


L. M. 
and T. 


s. 

Monos. 


Eos. 


P. N. 
Neut. 


s. 

Monos. 


L. M. 
andT. 


Eos. 


April 21st.. 


8,700 


















22d. . . 


10,700 


58.0 


2.7 


11.7 


27.7 


6.200 


1,250 


290 


2,960 


23d. . . 


6,000 


56.2 


2.0 


15.2 


26.2 


i 3.370 


910 


120 


1,570 


24th.. 


11,000 


60.4 


4.0 


13.2 


22.4 ! 


! 6,640 


1,450 


440 


2,460 


25th.. 


11,000 


57.2 


4.2 


18.6 


20.0 


6,290 


2,050 


460 


2,200 


26th.. 


9,600 


60.7 


5.3 


12.3 


21.7 


5,830 


1,180 


510 


2,080 


27th.. 


11,300 


63.0 


5.0 


17.0 


14.7 


7,120 


1,920 


560 


1,660 


28th.. 


12,700 


62.7 


4.0 


17.0 


16.3 


7,960 


2,160 


510 


2,070 


29th.. 


12,000 


67.0 


3.25 


15.25 


14.0 


8,040 


1.830 


390 


1,680 


May 1st . . 


10,700 


58.3 


4.0 


22.0 


15.7 


6,240 


2.350 


430 


1,680 


3d. . . 


13,000 


64.3 


4.0 


16,0 


15.7 


8.360 


2,080 


520 


2,040 


5th.. 


12,000 


64.7 


4.0 


16.0 


15.3 1 


7,760 


1.920 


480 


1,840 


7th.. 


9,300 


62.8 


4.0 


16.4 


16.8 1 


6,140 


1,530 


370 


1,560 


10th.. 


10,700 


60.4 


2.8 


16.4 


20.0 1 


6,460 


1,750 


300 


2,140 


12th . . 


11,000 


60.4 


3.3 


166 


19.6 


6.640 


1,820 


360 


2.160 


14th . . 


12,000 


58.8 


2.8 


18.8 


19.6 


7.060 


2,260 


340 


2,350 


17th.. 


9,000 


58.8 


3.6 


20.0 


17.0 


5.290 


1,800 


320 


1,580 



Brown's third case was studied in December, 1897. 

The blood (Table CXIII.) on admission showed forty-five per 
cent of eosinophiles, and this, as in the two previous cases, led to 
the diagnosis of trichiniasis and the subsequent confirmation of that 
diagnosis by the removal of a portion of muscle and the discovery 
of trichinae therein. 



Table CXIII.— Case III.— Blood Chakt. 



Date. 


Red blood 
corpuscles. 


Leuco- 
cytes. 


Per cent Per cent 
polymorpho-l large mono- 
nuclear Inuclears and 
neutrophlles. transitional. 


Per cent 
small mono- 
nuclears. 


Per cent 
eosino- 
philes. 


Dec. 22d . . 
23d .. 

27th . . 
Jan. 3d . . . 
7th . . 
10th . . 
14th . . 
22d . . . 


4,'700,b60 
4,300,000 

4*546, boo 


17",o66 
15,300 
12,000 
14,700 

13,666 
9,000 


48.4 
52.7 
. 42.4 
42.2 
31.6 
32.4 
35.2 
45.5 


4.7 
3.6 
4.0 
4.2 
4.4 
3.0 
4.0 
2.0 


1.5 
3.1 
5.6 
4.6 

19.0 
21.8 
23.4 
17.7 


45.4 
40.4 
45.0 
49.0 
44.6 
42.8 
37.2 
34.7 



This case was seen subsequently (July 10th, 1898) six months 
after the disappearance of all symptoms, and the following (?ior- 
mal) count was registered. 



TRICHINIASIS. 



499 



The count made on July 10th, 1898, was : 

Leucocytes (per cubic millimetre. ) 7,000 

Polymorphonuclear neutrophiles 68 per cent. 

Small mononuclears 23 " 

Large mononuclear and transitional forms 6 " 

Eosinophiles 3 

A fourth case was reported by the same writer in January, 1899 
{Medical News), The counts were as follows ; 



Date, 1898. 


Leuco- 
cytes. 


Per cent 
polymorpho- 
nuclear 
neutrophiles. 


Per cent 
small mono- 
nuclears. 


Per cent 
lar^e mononu- 
clears and 
transitionals. 


Eosino- 
philes. 


August 8th 

10th 

13th 

28th 

September 4th . . 
18th.. 
25th.. 

October 2d 

November 5th . . 
13th.. 
20th.. 


18,100 

'. ' 8,266 
. 7,900 

.' ' 9,606 

. 8,750 


43" 

45 

49 

55.2 

61.5 

54 

49 

64.5 

61 


' 7.3 
14.5 

18.5 

19.6 

16 

19.5 

40 

27 

27 


' i.'7 

2.5 
2.5 
2.5 
3 

4.5 


48 

48 

38.5 

30 

23.^ 

20 

24 
8.5 
5.5 
7.5 



In January, 1900, Blumer ' and Neumann report a " Family 
Outbreak of Trichinosis " including nine cases. The counts were 
as follows: 







Leuco- 
cytes. 


Per cent 


Per cent 
transi- 


Per cent 
small 

mononu- 
clears. 


Per cent 


Name. 


Date. 


polynu- 
clears. 


tionals and 
large mo- 


eosino- 
philes. 










nonuclears. 




Casel. D. V 


March 8th 
13th 


19,000 
18,000 


47.4 


8.8 


3.2 


40.6 




19th 


12,400 


50.6 


4.4 


7.6 


37.4 




26th 


20,600 


69.6 


5.6 


10.0 


14.8 




April 1st 


13,200 


73.0 


5.0 


12.0 


10.0 


Case 2. Mary C 


March 8th 


8,400 


61.4 


6.8 


10.0 


21.S 




12th 


20,000 


51.6 


10.4 


14.6 


23.4 




19th 


17,200 


39.0 


4.8 


16.2 


40.a 




26th 


12,000 


48.0 


6.6 


14.6 


30.8 




April 1st 


16,000 


42.0 


4.3 


12.2 


41.5 


Cases. A.V 


March 8th 


24,000 


56.8 


6.4 


3.6 


33.3 




12th 


14.000 


52.4 


3.8 


7.8 


36.0 




19th 


20,600 


64.4 


2.8 


5.2 


27.6 




36th 


18,000 


66.25 


4.0 


6.5 


2;}.2;> 




April 1st 


15,200 


56.6 


4.4 


10.4 


28.() 


Case 4. Mrs. D. V. 


March 8th 


8,000 


51.0 


7.8 


7.6 


33.6 




12th 




50.8 


4.2 


18.0 


27.0 




19th 


12,400 


50.6 


5.6 


11.0 


32.8 




26th 


13,200 


54.0 


5.0 


11.0 


30.0 



^ American Jour, of the Med. Sciences. 



mo 



SPECIAL PATHOLOGY OF THE BLOOD. 



Name. 


Date. 


Leuco- 
cytes. 


Per cent 
polynu- 
clears. 


Per cent 
transi- 
tionals and 
large mo- 
nonuclears. 


Per cent 
small 

mononu- 
clears. 


Per cent 
eosino- 
philes. 


Cases. T. V 

Case 6. R.G 

Case 7. J. V 

Cases. R. V 

Case 9. Mrs. R. G. 


March 8th 
12th 
19th 
26th 

March 9th 
19th 
26th 

April 9th 

March 12th 
19th 
26th 

April 1st 

March 12th 
19th 

26th 
April 1st 

March 9th 
19th 
26th 

April 9th 


8,(XHJ 
14,000 
18,600 
14,600 

14,000 

8,()00 
6,(XX) 

16,000 

23,fKX) 

16,(KMJ 

8,6<J0 

10,000 

12,tiO0 
12,600 

12,400 
15,200 
12,600 
10,000 


32.6 
49.0 
41.4 
35.0 

45.6 
45.4 

48.8 
64.4 

44.0 
53.2 
41.6 
39.3 

39.0 
36.0 
55.5 
44.0 

48.0 
59.2 
67.0 
74.0 


10.8 
4.2 
5.6 
3.5 

15.16 
2.6 
5.0 

6.8 

9.2 

2.8 
6.0 
9.0 

6.0 
4.8 
5.5 
7.0 

9.6 
4.0 
6.5 
5.0 


6.4 
15.0 
10.8 
18.5 

7.0 
6.0 
10.8 
12.2 

15.8 
6.2 
13.0 
16.1 

20.0 
8.5 
9.25 
5.5 

25.4 

16.8 
13.0 
13.0 


5fJ.2 
31.8 
42.2 
43.0 

32.16 
46.0 
a5.4 
16.6 

31.0 
37.0 
39.4 
a5.6 

a5.o 

50.4 
29.75 

38.0 

17.0 
20.0 
13.5 

8.0 



My own experience is as follows 



Case. 


Date. 


Red 

cells. 


White 
cells. 


i 


ST; 

4 


li 


^1 
^1 


• 


^1 


1 


September 3()th, 1897. 

November 4th 

September 6th, 1899.. 

10th 

13th 

15th 

19th 

22(1 

September 29th 

November 4th 

10th 

29th 

First day 


5,120,000 
4,900,000 



4,712,000 
5,728",660 


11,000 
7,000 
1,410 
25,000 
23,000 
21,000 
11,000 
14,000 
10,900 

ih'M 

11,600 
10,500 
13,200 
16,100 
15,200 
17,900 


70 


39.0 
36.5 
59 

71.2 

71.2 

.53.6 

.58.9 

67.8 

65 

60 

75 

39 

52 

39 

54 


31.0 
46 
3 

7 

9.6 
23 
32 
24.4 
11 
16 
18 
23 
13 
37 
22 


28.0 

17 

34 

19 

16 

23 
9.1 
7.8 

22 

24 
7 

37 

a5 

23 
24 


2.0 
.5 

2 

2 

2.0 
.4 

1.4 

.6 

1 




2 


2.0 
.8 

1.2 

6 


2 


S 




Fourth day 




Seventh day 

Tenth day 


4 


4 


Thirteenth day 

Fifteenth day 








Atkins 


on ^ reports one 


case as 


follo^^ 


rs: 





















J 


-kJ c5 


5C 


r; 




Date. 


Red cells. 


White 
cells. 


S be 




is 

a; o- 


11 












p...^ 
% 






January 14th, 


1899 








31.1 


9.5 


58.5 


18th. 




5,528,000 


28,000 


93 


21.5 


24.2 


54.3 


25th 








25.6 
43.4 


39.4 
16.6 


as 


31st 


40 



Phila. Med. Journal, June 3d, 1899. 



TRICHINIASIS. 



501 



Gwyn ' reports a similar case in which the eosinophiles ranged 
from 33 to 65.9 per cent during a period of six weeks. The leuco- 
cytes were at one time 17,000 per cubic millimetre 

Stump ^ found 52 per cent of eosinophiles in his case. 

W. W. Kerr ^ puts the following figures on record : 



Case 1. 



Case 2. 



Date, 



Nov. Oth 

lOth 

11th 

13th 

15th 

16th 

17th 

18th 

20th 

22d 

23d 

27th 

29th 

Dec. 3d 

8th 

11th 

13th 

Nov. 17th 

18th 

20th 

21st 

22d 

23d 

24th 

25th 

27th 

29th 

Dec. 1st 

2d 

3d 

5th 

6th 

8th 

9th 

11th 

13th 



Red cells. 



5,800,000 
4,888,000 



White 

cells. 



4.250,000 



3,340,000 



25,000 
20,600 



13,000 



10,000 



20,000 



3,300,000 I 17,000 



Per 

cent 
hgemo- 
globin. 



85 



100 



77 



Per 

cent 
polynu- 
clear. 



52.0 
49.4 
53.6 
41.7 
36.6 
35.0 
47.0 
46.5 
48.0 
50.8 
52.4 
40.0 
22.5 
28.7 
10.6 
23.6 
23.9 
41.6 
53.2 
37.0 
34.0 
20.0 
15.3 
10.4 
10.5 
17.0 
6.5 
4.2 
11.4 
10.0 
14.8 
0.75 
3.1 
10.9 
11.2 
13.1 



Per 
cent 
small 
lympho- 
cyte; 



1.0 

3.6 

5.9 

4.3 

7.7 

5.3 

8.5 

10.5 

8.0 

2.0 

10.9 

15.0 

19.8 

2.8 

6.0 

13.2 

9.8 

16.4 

18.9 

11.0 

11.0 

8.2 

5.7 

7.2 

6.4 

6.4 

3.9 

30 

10.1 

7.3 

8.0 

5.0 

9.5 

3.6 

18.2 

9.4 



Per 
cent 
large 
lympho- 
cytes. 



1.0 
2.8 
2.2 



7.6 

15.5 

10.9 

8.0 

14.0 

6.8 

4.0 

14.6 

10 6 

14.8 

14.3 

5.6 

23.9 

6.0 

6.0 

4.0 

3.2 

2.1 

1.4 

2.4 

9.1 

8.4 

6.1 

4.9 

6.1 

7.0 

18.8 

8.6 

9.0 

14.2 

9.3 



Per 

cent 
eosino- 
philes. 



42.0 
44.2 
38.3 

54.0 
52.0 
52.5 
29.0 
31.1 
34.0 
32.0 
38.3 
41.0 
43.0 
57.8 
68.7 
48.9 
60.7 
18.1 
21.9 
45.0 
50.0 
68.0 
76.9 
81.0 
80.7 
66.9 
81.2 
86.6 
73.5 
76.6 
70.2 
76.0 
78.8 
72.7 
56.4 
68.2 



Harlow Brooks * examined the blood in one case, and found at 
the time of admission to the Belle vue Hospital (February 2d, 1900) 

'Centralbl. f. Bakt., vol. xxvi., No. ii. 

2 phiia. Med. Jour., Jime 17th, 1899 

3 Phila. Med. Journal, August 25th, 1900. 

4 Med. Record, May 19th, 1900. 



502 SPECIAL PATHOLOGY OF THE BLOOD. 

18,000 leucocytes, with 10 per cent of eosinophiles; on February 
12tli, 1900, 44 per cent of eosinophiles; thence a steady increase 
up to 83 per cent, followed by a decline, until on JNIarch 14th 15 
per cent of eosinophiles was present. Many of the granules were 
smaller than those of normal eosinophiles, but there was no evidence 
of forms transitional between eosinophiles and neutrophiles.' 

V. P. Kinnicutt^ reported a similar case, and H. C. Gordinier'" 
mentions two, one presenting 77 per cent, the other 29.9 per cent 
of eosinophiles. 

In one of my cases^ when the symptoms disappeared, the eosino- 
philes gradually returned to normal. Two j'ears later a relapse 
occurred — not a reinfection — and the eosinophiles became increased 
as before — later decreasing again as the patient recovered from this 
recrudescence of the disease. 

Si()U7n((7'//. 

In active cases eosinophilia is the rule. It probably occurs dur- 
ing some part of the course of all infections, but in those of long 
standing or quiescent it may disappear. With a recrudescence of 
the disease the eosinophilia may reappear, its duration depending 
probably on the degree of activity of the reactive process in the 
muscles. 

Diagnostic Value. 

The characteristic blood lesions change trichiniasis from the posi- 
tion of a disease very difficult and uncertain of diagnosis (without 
excision of a bit of muscle) to one whose recognition is usually easy. 
Cases formerly diagnosed as typhoid, muscular rheumatism, or neu- 
ritis now find their true interpretation. 

STRONGYLOIDES INTESTIXALIS. 

Teissier * reports finding the embryos of this nematode in the 
blood of a patient in Guiana whose stools swarmed with the same 
organism. Bucklers has recorded the following data: 

' Manj^ additional cases supporting these have been reported in 1901 and 
1902. Drake (Journal Med. Research, 1902) and Da Costa {Loc. cit., p. 435) 
have shown that it is possible, though exceedingly rare, to have trichiniasis 
M^thout eosinophilia. Very possibly it may be true that in long-standing 
cases the eosinophilic reaction dies out as it does in uncinariasis. 

2 Practitioners' Soc, February 2d, 1900. 

2 Medical Record, October 20th, 1900. 

^ Teissier: Comp. rend. d. I'Acad. des Sciences, 1895, No. 3. 



STRONGYLOIDES INTESTINALIS. 503 

Strong YLOiDES Intestinalis, 

Per Cent. 

Eosinophiles 13.5 

Polyuuclears 38. 5 

Lymphocytes and transitional 48 

STRONGYLOIDES InTESTINALIS WITH UnCINARIA. 

Eosinophiles 15 

Polynuciears 58 

Lymphocytes and transitionals 27 

P. K. Brown ' in a case of strongyloides intestinalis with au- 
topsy reports : (a) Red cells, 3,882,000; white cells, 9,400; haemo- 
globin, 65 percent; polynuciears, 71.3 per cent; lymphocytes, 22.3 
per cent; eosinophiles, 6.3 per cent, (b) Strongyloides with un- 
cinaria and tricocephalus : Leucocytes, 7,000; eosinophiles, 5 per 
cent, (c) Strongyloides with uncinaria and tricocephalus : Leuco- 
cytes, 7,600; eosinophiles, 10 per cent. 

The following data are from Biiklers : 



Eosinophiles 

Polynuciears 

Lymphocytes and tran- 
sitionals 



Case 



Oxyuris and 
ascarides. 



19 per ct. 
53 " 

28 « 



Case II. 
Oxyuris. 



16 per ct. 
63 " 

21 " 



Case III. 

Oxyuris with 
ascarides and 
trlchoeephalus. 



8 per ct. 
69 " 

23 " 



Case IV. 

Oxyuris with 
ascarides, trlch- 

ocephalus and 
Teenia saginata 



5.7 per ct. 
63.3 " 

31.0 " 



Table CXIV. — Ascarides (alone). 



Eosinophiles 

Polynuciears 

Lymphocytes and tran 
sitionals 



Case I. 



7.4 per ct. 
55.0 " 

37.6 " 



Case II. 



8.5 per ct. 
55.0 " 

26.5 " 



Case III. 



9.8 perct. 
50.0 " 

40.2 " 



Case IV. 



1.8 per ct. 



Longridge (Brit. Med. Jour., November 8th, 1902), in a case 
of tuberculous peritonitis with ascaris lumbricoides, records : Eed 
cells, 4,800,000; leucocytes, 12,400; eosinophiles, 6 8 per cent. 

The report of the Jenner Hospital at Berne (1890) includes the 
account of a case in which ascaris was present in large numbers. 
The blood showed but 2,480,000 red cells before the expulsion 
of the parasite by santonin; two weeks later the red cells were 

4,200,000. 

1 Brown: Boston Med. and Surg. Jour., May 28th, 1903. 



^04 SPECIAL PATHOLOGY OF THE BLOOD. 

Table CXV.— T^nia (Bucklers). 



Case I. 



Taenia 

Solium. 



Case II. 



Taenia 
Saginata. 



Case III. 



Taenia 
Nana. 



Case IV. 



Taenia 
Saginata. 



CaseV. 



Taenia 
Saginata. 



Eosinophiles 

Polynuclears 

Lymphocytes and 
transitionals 



8.2 p. ct. 
49.4 " 

42.4 " 



5.5 p. ct. 
65.0 " 

29.5 " 



7.0 p. ct. 
42.0 " 

51.0 « 



.0 p. ct, 



10.0 p. ct. 



In a case of infection of the skin, with taenia solium ("La- 
drerie ") Achard and Loeper ' found eleven per cent of eosinophiles 
(649 absolutely). Marie and Guillain^ in a similar case found nor- 
mal blood. 

In ordinary intestinal infections with tapeworm, many of which 
I have examined, eosinophilia is not usually to be found at the time 
when the patients present themselves for treatment. 

T^NIA INERMIS. 

Launois ^ and Emile-Weil found eosinophilia throughout the 
of infection. 

AMCEBIC DYSENTERY. 

Amberg * noted in five cases the presence of eosinophilia with 
leucocytosis and anaemia. Futcher ' found the average leucocyte 
count in 43 cases to be 10,600 with no increase of eosinophiles in 
" a number " of cases examined with reference to this point. 

TRICOCEPHALUS DISPAR. 



P. K. Brown (loc. cit.) reports that in twelve cases in which this 
parasite was the only one found in the stools the eosinophiles rarely 
fell below five per cent. 

Ostrovsky ^ has recorded a case of fatal anaemia apparently due 
to this parasite. 

1 Achard and Loeper: Soc. Med. d. Hop., 1900, p. 8C7. 

2 Marie and Guillain: Ibidem, November 8th, 1901. 
2 Launois: Sem. Med., November 12th, 1902. 
^Amberg: Johns Hopkins Bull., December, 1901. 

5 Futcher: Journ. Am. Med. Assn., August 22d, 1903. 

« Ostrovsky: Ref. in N. Y. Med. Jour., 1900, vol. 72, p. 826. 



CHAPTER XIII. 
DISEASES OF THE SKIN. 

DERMATITIS PIERPETIFORMIS. 

According to Leredde, who has written extensively on the con- 
dition of the blood in this disease, the following terms are in use to 
designate the same actual set of facts: Dermatitis herpetiformis; 
Dtihring's dermatosis; Polymorphous pruriginous dermatitis; Hy- 
droa (Unna); Pemphigus vegetans (Neumann); Hallopeau's infec- 
tious dermatosis; Herpes gestationis. 

In all of this he finds marked constant eosinophilia, averaging 
16 per cent. At times the percentage may reach 25 or 30. 

My own experience includes three cases, one diagnosed as der- 
matitis herpetiformis, the others as hydroa sestivale. The counts 
were as follows : 



Case I. 
Dermatitis herpe- 
tiformis. 



Case 11. 
Hydroa sestivale. 



Case in. 
Hydroa aestivale. 



Polynuclear neutrophiles 

Small lymphocytes 

Large lymphocytes. .. 

Eosinophiles 

Myelocytes 



47 per cent 
25 " " 
8 " " 
19 " " 

1 " " 



40.0 per cent 
42.4 " " 

8.6 " " 

8.2 " " 



34 per cent 
43 " " 

8 " " 
15 " " 



Brown ^ reports the following figures in a case of dermatitis her- 
petiformis (twenty-seven years' duration) : 





June 12th, 
1899. 


June 17th, 
1899. 


June 25th, 
1899. 


June 30th, 
1899. 


Sept. 5th, 
1899. 


Red cells 


5,128,000 
14,000 







5,163,000 
9,000 


5,808,000 


White cells 


9.700 






Polynuclear neut 

Lvrnphocvtes 


Per cent. 
32.8 
38.0 
29.2 


Per cent. 
31.3 
24.4 

44.3(0 


Per cent. 
29.25 
34.5 
36.25 


Per cent. 
39.25 
21.5 
39.25 


Per cent. 
36.0 
34.4 


Eosinophiles 


29.3 







Soc. for Original Research, Conn., October 12th, 1899. 



506 



SPECIAL PATHOLOGY OF THE BLOOD. 
Table CXVI. — Erythema Multiforme. 









White 


Per cent 






Age. 


Red cells. 


cells. 


haemo- 


Remarks. 


z 








globin. 




1 


29 




19,700 

20,400 
12,900 




First day. Temperature, 102'; ery- 
thema nodosum and multiforme. 
Second day. Temperature 103'. 
Sixth day. Temperature 98'. 


2 


27 




18,400 
6,800 




Temperature 104'. 

Temperature 104°, third day. Eosino- 
philes not -h. 


3 


18 




11,400 


65 


Nodosum. 


4 


43 





9,200 


70 




5 


17 




8,200 


. . 


Temperature 102"'. 


6 


29 





7,000 


60 


August 8th. Diff. count, 500 cells: 
Polynuclear, 75.5 per cent; lympho- 
cytes, 20; eosinophiles, 4.5. 

September 2d. Polynuclear, 73 per 
cent ; lymphocytes, 25 ; eosinophiles, 
2. 

Diff. count, 425 cells. Polynuclear, 69 


7 


24 




6,150 














per cent; lymphocytes, 30; eosino- 






1 




philes, 1. 



HERPES TONS TRANS. 

Mark A. Brown' records this blood count : White cells, 10,700; 
of these, there were eosinophiles, 25.2 per cent; polynuclears, 45.6; 
lymphocytes, 29.2. 

HERPES ZOSTER. 



Sabrazes and. Mathis {Rev. de Med., 1901, p. 251) studied seven 
cases. They found no changes in the red cells or in the haemoglo- 
bin. There was leucocytosis increasing until the third day, then 
decreasing until the period of desiccation, when a slight secondary 
rise occurred. In two weeks the blood was normal. On the first 
day the counts were from 11,000 to 16,000; on the third they aver- 
aged 17,900, on the fifth, 13,000. Throughout this period there 
was an increase of polynuclear cells and eosinophiles with a few 
mj^elocytes. The eosinophiles reached their maximum in the des- 
quamative period — 8 to 20 per cent (800 absolutely). 

Bettmann (loc. clt.) had previously reported eosinophilia in a 
single case. 

1 In Conn. Lancet-Clinic, December 22d, 1900 



PSORIASIS. 



507 



ACUTE ECZEMA. 



6 
2; 


Age. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Remarks. 


1 


22 




15,000 

13,200 
10,200 


95 


April 3d. Diff . count, 300 cells : Poly- 
nuclear, 74. 7 per cent ; small lympho- 
cytes, 16.6; large lymphocytes, 5.3; 
eosinophiles, 3.4. 

May 5th. Diff. count, 400 cells: Poly- 
nuclear, 63. 7 per cent ; small lympho- 
cytes, 26; large lymphocytes, 7; 
eosinophiles, 3.3. 

May 7th. 

May 19th. 



The above data are from a recent case at the Massachusetts 
Hospital. Stengel and White (loc. cit.) record 7.9 per cent of 
eosinophiles in a single case. 

CHRONIC ECZEMA. 

Thomas K. Brown ' reports a case of chronic eczema, studied at 
the Johns Hopkins Hospital, in which three counts showed 22.6 per 
cent, 24 per cent, and 22,7 per cent of eosinophiles. 

Zappert {loc. cit.) notes a similar case with 8,600 leucocytes per 
cubic millimetre, 9.9 per cent of which were eosinopiles (843 abso- 
lute). Bettmann {loc. cit.) records 45 per cent eosinophiles in a 
similar case. 



SCLERODERMA. 

Two cases in Zappert's series showed: 

Leucocytes. 

1 16,690 9.4 

2 9,000 7.7 



Per cent 
eosinophiles. 

(1,580 absolute.) 
( 694 " ) 



PSORIASIS. 

One of Zappert's cases had 8,600 leucocytes, with 9.8 per cent 
of eosinophiles (850 absolute). Bettmann confirms this. 
1 Jour, of Exp. Med., vol. iii. p. 320. 



508 



SPECIAL PATHOLOGY OF THE BLOOD 



PEMPHIGUS. 



Reporter. 


No. 


Red cells. 


White cells. 


Per cent eosinophiles. 


Zappert. . . 
Zappert. . . 
Zappert. . . 
Andry 


1 
2 
3 
4 


3.952.000 
3,940,000 
4,120,000 


5.300 
10,600 

1,640 
13,000 


33.0 (1,750 absolute). 

14.1 (1,500 absolute). 

29.2 (4,800 absolute). 
15-24 (1,750-3,120 abs.) 



This is confirmed by Neusser ^ and Canon/ and Bettmann."* 
Brown * in three cases found 3 per cent (360 absolute), 5 per cent 
(750 absolute), and in the third, no increase. Coe ^ in one case 
found 50 per cent, or 6,000 absolute. 



LUPUS. 

Two cases (Zappert). Bettmann (loc. cit.) confirms. 



Cases. 


Red cells. 


White cells. 


Per cent eosinophiles. 


1 

2 


3,224,000 
4,250,000 


9,200 
9,450 


12.2 (1.126 absolute). 
7.3 (696 absolute). 







DRUG ERUPTIONS. 

Iodide of potash " eruptions have been found by two observers 
to be associated with eosinophilia (14 per cent). 

Mercurial dermatitis,' and the eruptions produced by picric-acid 
solution ^ applied externally for a burn, have likewise produced 
eosinophilia (15 per cent) with the latter. Zappert has seen a simi- 
lar result from the rash of sodic salicylate, and in Ehrlich and Lin- 
denthal's case of nitrohenzol 2^oisoning (vide su2yra, page 410) the 
same thing was observed. 

Brown's case * of acute acetanilid poisoning with 12 per cent of 

1 Neusser: Wien. Idin. Wocli., 1892, p. 41. 

2 Canon: Deut. med. Woch., 1892, p.. 206. 
^ Bettman : Loc. cit. 

4 Brown: Maryland Med. Jour., April, 1901, and July, 1902. 
^ Coe: Amer. Med., June 28tli, 1902. 

«Lerrede: Presse Med., 1898, No. 106. Seifert and Wurzburg: Physic- 
Med. Gesellsch. February, 1902. 

^Hoffman: Berl. klin. Woch., September 29th, 1902. 
8 Achard and Clerk: Gaz. Hebd., 1900, No. 81. 



DERMATITIS EXFOLIATIVA. 



509 



eosinophiles (3,600 absolute), though without eruption, probably 
belongs in this class, as does that of von Noorden, previously men- 
tioned (^vide su])ra, page 109). 

In hulloiis dermatitis following vaccination Bowen ^ records : 



Case. 


Red cells. 


White 
cells. 


Per cent 
haemo- 
globin. 


Per cent 

poly- 
nuclears. 


Per cent 
lympho- 
cytes. 

19 
16 
30 


Per cent 
eosino- 
philes. 


Remarks. 


1 






65" 


63 
71 

48 


18 
13 
31 


Nov. 28th, 1899. 


2 


5,100,000 


7,400 


Dec. 16th, 1900. 













EPIDERMOLYSIS BULLOSA HEREDITARIA. 

Columbini "^ found 8 to 10 per cent of eosinophiles, and Brown ^ 
97 per cent (1,100 absolute). 

XERODERMA PIGMENTOSUM. 

Okamura {Arch. f. Dermat. u. Syph., February, 1901) notes a 
leucocytosis averaging over 40,000 in three cases, in two of which 
there was moderate eosinophilia. 

DERMATITIS EXFOLIATIVA. 

Pitkianen {loc. cit.) finds a considerable eosinophilia from the 
first day of the disease and contrasts the blood with that of scarlet 
fever in which the eosinophilia comes later and is less marked. 

^ Bowen: Jour, of Cut. and Gen. -Urin, Diseases, September, 1901. 

2 Columbini: Monatsch. f. pract. Dermat., May 15th, 1900. 

3 Brown: Maryland Med. Journ., April, 1901, and July, 1902. 



CHAPTER XIV. 

THE BLOOD IN PREMATURE INFANTS. 

Engel ("Leitfadeii z. klin. Uiitersuch. des lUutes," Berlin, 
1902) studied the blood of an embryo 23 cm. long, the heart still 
beating. He found: Red cells, 3,300,000; white cells, 12,500; 
lisemoglobin, 80 per cent (i.e., notably high). There were 27,500 
nucleated red cells per cubic millimetre, mostly normoblasts, with 
polychromatophilic protoplasm. Great variations in size and stain- 
ing reactions were also present in the non-nucleated red cells. 

Among the leucocytes w^ere many myelocytes and mononuclear 
eosinopliiles, Fischl (Zeitsch. f. He'dk., 1892) believes that the 
eosinopliiles do not enter the blood until after the seventh month of 
pregnancy. 

THE BLOOD IN INFANCY. 

I. All the signs hy which sickness is shown in the hlood of adults 
are exaggerated in children. Their blood is apparently more sensi- 
tive to the action of any morbid influence. Causes leading to but 
slight anaemia or leucocytosis in the adult produce grave anaemia 
and very marked leucocytosis in children. Into the reasons for this 
I shall not attempt to enter. The increased toxicity of their serum 
compared to that of adults, and the relatively recent establishment 
of the functions for producing and destroying blood have been sug- 
gested as explanation. 

Comparatively slight hemorrhages, gastro-intestinal or respira- 
tory disorders, which would not impoverish an adult's blood may 
produce considerable anaemia in a young child. 

II. All forms of anaemia in infancy are apt to be associated with 
enlarged spleen. 

III. I have already alluded to the polycythaemia and leucocy- 
tosis of the new-born, and the gradual fading out of these relative 
abnormalities as the child grows up. Carstanjen's ' fine studies 

lOarstanjen: Yahrb. f. Kinderh., vol. 52, 1900. 



THE BLOOD IN INFANCY. 



511 



lead him to the following conclusions : At the moment of birth and 
for the next twenty-four hours, the infant's blood contains about 
seventy-five polynuclear cells in every one hundred leucocytes. 
After the first day the per cent of polynuclear cells rapidly sinks, 
while the lymphocytes increase, until by the sixth or ninth day of 
life the two forms are about equally numerous. By the twelfth day 
the blood has taken on the picture which it retains for the first ten 
months of life — i.e. : Polynuclears, 36 per cent; lymphocytes, 45; 
large mononuclears, 1; transitional forms, 18; eosinophiles 1 to 3 
Mast cells and myelocytes, very scanty. 

From this time on the polynuclear cells gradually rise and the 
lymphocytes fall until the fifth year. During the first five years 
Carstanjen's averages are as in the following table. ^ 



Year. 


Per cent 
polynuclear. 


Per cent 
lymphocytes 

and 
transitionals. 


Per cent 
eosinophiles. 


One to two 


42 

48 
52 
61 


55 

48 
43 
33 


3 


Two to three 

Three to four 


4 
5 


Four to five 


6 







After this period the percentages are practically the same as in 
adult life. 

As regards the red cells we need to remember that in the blood 
of the new-born there are normally very great variations in the 
size, shape, and staining reactions of the red cells, and that deficient 
rouleaux formation is the rule. Normoblasts are usually present m 
the earliest days of life and megaloblasts are occasionally found, 
but in healthy children both varieties are very scanty after the third 
day, and never occur after the seventh month. ^ In Warfield's cases 
the normoblasts averaged about 11,000 per cubic millimetre on the 
first day. In judgments as to the presence or absence of leucocyto- 
sis in infancy, these physiological variations are too often lost sight 
of, especially as the proper leucocyte count for any given infant de- 

1 The figures of Japha (Jahrbuch f. Kinderh., 1901, vol. 53, p. 179), Kar- 
nizki (Archiv f. Kinderh., 1903, p. 42), and Warfield (Am. Med., 1902, vol. 
xxxvi., p. 457), are practically identical with the above. Japha found the 
average total leucocyte count to be 13,560 in twenty two healthy infants 
under one year. 

2Karnizki: Arch. f. Kinderheilk . , 1903, p. 42. 



512 SPECIAL PATHOLOGY OF THE BLOOD. 

pends not simply on its age but on tlie backwardness or forward- 
ness of its development. As with the fontanels, the growth of the 
blood toward adult conditions may be retarded by congenital weak- 
ness (infantile atrophy, marasmus) or inherited disease (tubercu- 
losis, syphilis) as well as by acquired sickness (rickets). 

Under the influence of any of these drawbacks a sick child's 
blood may be no further developed at three years than that of a 
healthy child of eighteen months. 

IV. When Ave remember that in early infancy the leucoc3'tes 
differ from those of adults not only in number but in that the lym- 
phocytes are relatively more numerous (" lymphocytosis of infancy ") 
we shall understand that any influence like rickets or syphilis, which 
retards development, will show Ij^mphocytosis together with the 
increased leucocyte count. Qualitatively as well as quantitatively 
the blood reverts to a more infantile condition. 

Under pathological conditions the red cells revert to the earlier 
type just described, and deformed or nucleated corpuscles are plen- 
tiful. This is more marked than in anaemia of the same grade 
occurring in adults. An anaemia that shows but thirty nucleated 
erythrocytes per cubic millimetre in an adult might show ten times 
that number in a child. 

V. As I said before, all blood changes are exaggerated in in- 
fancy. This includes such physiological changes as the digestion 
leucocytosis or that following cold bathing, and changes in the de- 
gree of dilution or concentration of the blood seem to be similarly 
exaggerated, as is seen, e.g.^ in the physiological variations in the 
specific gravity of the serum (Hock and Schlesinger ^). According 
to Head ^ disease such as typhoid meningitis, pneumonia, or appen- 
dicitis, affect the blood of children (after the second year) exactly 
as they do the blood of adults. 

YI. The hcemoglohin, though relatively high at birth and for 
the first few ^veeks, is lower than that of adults during the rest of 
childhood. The high percentages of the earliest weeks are not due 
to a polycythaemia, but to a genuine increase of haemoglobin in the 
individual cells (Schiff ^), color indexes being often over 1. 

It is indispenable, therefore, that we should know the age and 
degree of development of a child before we can draw accurate infer- 

^ Hock and Schlesinger: Centralbl. f. kiln. Med., 1891. 
^ Head : Paediatrics, February, 1900. 
^Schiff: Zeit. f. Heilk., vol. xi., 1890. 



THE ANEMIAS OF INFANCY. 513 

ences from its blood. In many of the cases reported in literature 
we are unable to judge whether the blood condition is pathological 
or not, because the age of the child is not given. For example, v. 
Limbeck ' notes a case of acute gastritis reported by Fischl - as hav- 
ing an unusually high percentage of lymphocytes (59.4 per cent). 
But this is physiological in the first days of life, and may have 
been so in this case, the age not being given. 

Observations of this sort should always represent a comparison 
between the conditions present before and during sickness in ques- 
tion. 

Bearing these general considerations in mind, we shall be better 
able to find our way among the complications and perplexities of 
the blood conditions in infancy. 

THE SUMMER DIARRHCEAS OF INFANCY. 

Japha {loc. cit.) in gastro-mtestinal catarrh (foul mucous stools 
and fever) found an increase in the polynuclear cells (47 to 55 per 
cent, normal = 42 per cent) which raised the total count to a vary- 
ing extent — once to 36,000. 

Ill follicular enteritis (blood and mucous stools with wasting and 
with or without fever) practically the same conditions obtain (poly- 
nuclears average 60 per cent; lymphocytes, 35 per cent; total count, 
15,000 to 38,000). 

In cholera infantum a higher leucocyte count occurred — 51,000 
to 54,000 — with polynuclear ^5 per cent and lymphocytes 25 per 
cent on the average. 

Knox and Warfield ' found practically similar results. They 
note also that eosinophiles are often diminished or absent in each of 
these groups of cases. The degree of leucocytosis seems to be of 
no diagnostic or prognostic value. 

THE ANEMIAS OF INFANCY". 

As above mentioned, anaemic infants are apt to have enlarged 
spleens This may be due either to the anaemia or to some disease 
accompanying or underlying the anaemia {e.g. , rickets, syphilis). It 
seems more probable that the hypertrophy is not directly or exclu- 
sively dependent on the anaemia, inasmuch as similar blood changes 

' V. Limbeck. Loc. cit., p 373. 

2 Fischl: Zeit. f. Heilkuude, 1892. 

3 Knox and Warfiekl. Johns Hopkins Bull., July, 1902. 

33 



514 SPECIAL PATHOLOGY OF THE BLOOD. 

are found without splenic enlargement. By far the greater number 
of reported cases of severe infantile anaemia are accompanied or 
caused by such diseases as rickets and hereditary syphilis, both of 
which may cause splenic hyperplasia even when no anaemia is pres- 
ent. It seems probable that the anaemia and the enlargement of 
the spleen are alike symptomatic of an underlying disorder. 

It does not seem to me that we can recognize in the blood of in- 
fants any of the well-delined types of anaemia which we have learned 
to correlate in adults with a detinite set of symptoms and a definite 
prognosis. All such distinctions as pernicious anaemia, secondary 
anaemia, splenic anaemia, or chlorosis are blurred in infancy. A 
blood which in adult life would mean pernicious anaemia, and so 
death in ninty-nine per cent of the cases, is compatible with a speedy 
and permanent recovery in infancy. 

In the midst of this confusion we may note the following praise- 
worthy efforts to secure order. 

1. Some writers (e.y., Luzet') divide the anaemias of infancy 
into two classes : those with splenic enlargement and those without 
it. Luzet considers that the former class is severer than the latter 
and more apt to show large numbers of nucleated red corpuscles 
than those with normal-sized spleens. This classification, however, 
does not always hold. We may have very severe anaemia without 
splenic enlargement and splenic enlargement with slight anaemia, 
and the presence or absence of numerous nucleated red corpuscles is 
governed by conditions other than the size of the spleen. 

2. Another classification of children's anaemias was proposed in 
1892 by Monti and Berggrlin (" Die chronische Anamie im Kindes- 
alter," Leipsic, 1892). They divided the cases into the wild and 
the grave J each group being subdivided into those with leucocytosis 
and those without it. 

f -^\•^A _ 5 With leucocytosis. 
SecoBda,,. a„.mia of infancy = \ " '_ \ ^i'tr^eucoeS^'^- 

^iTidve _ -j •^itjjout leucocytosis. 

They rightly discard the term "splenic anaemia," corresponding 
as it does to no single set of blood changes. The above classifica- 
tion puts pernicious anaemia, leukaemia, and anaemia infantum pseu- 
doleukaemica (v. Jaksch) in a different category. 

(a) Mild cases of secondary anaemia show no deformities in the 

^ Luzet; Diss., Paris, 1891. 



THE ANEMIAS OF INFANCY. 



515 



shape or size of the red cells. The color index may or may not be 
low. The cases with leucocytosis are much more numerous than 
those without it and more apt to have a low color index; in other 
words, the loss of corpuscle substance is greater and the cases are 
approaching the imaginary boundary between "mild" and " grave. ^' 

(b) The grave cases have poikilocytosis, and of course a greater 
reduction of corpuscle substance. 

" Chlorotic " conditions, and most but not all those with enlarged 
spleen, come under this heading; also most of those due to heredi- 
tary syphilis, prolonged diarrhoea, and rickets. 

In 1894 Monti ' gave the following classified lists of the com- 
monest antecedents of secondary anaemia in infancy : 



1. Congenital, 
due to. . . 



2. Acquired 



Syphilis, 
Tuberculosis, 
Malaria, etc. 



In the mother during pregnancy. 



f From navel. 
1 TTPTTirrrhflD-P j After circumcision. 

-''^^^- I Scurvy, purpura, haemophilia, Werlhof's 
[ disease, melaena. 
f Inanition. 
Bad hygiene (lack of light, air, etc.). 
Post-febrile. 
I Nephritis, diarrhoea, serous effusions. 
^ 2. Other causes. ^ Syphilis. 
Rickets. 
Suppuration. 

Diseases of liver, spleen, bone, or lymph 
i^ glands. 



He points out that cases with leucocytosis are usually graver than 
those without it and may develop into pernicious anaemia; also 
that the presence of leucocytosis does not point to malignant disease, 
suppuration, or any of the causes which usually account for it in 
adults. 

Grave cases with leucocytosis in infants under twelve months are 
apt to develop into the anaemia infantum pseudoleukaemica, or into 
true leukaemia or pernicious anaemia. 

On the whole, the division of Monti and Berggriin seems nuu*h 
better than that according to the particular causes, (>.(/., "rachitic 
anaemia," "syphilitic anaemia," etc., for there is no particular set 
of blood changes that follows rickets, syphilis, or any other disease. 
In connection with various diseases of infancy, and particularly 



Wiener med. Woch., 1894. 



516 SPECIAL PATHOLOGY OF THE BLOOD. 

with those last named, we may have anaemia of any grade of severi- 
ty, from that reducing the red cells to 4,000,000 down to cases with 
only 500,000 red cells per cubic millimetre or even less. The worse 
the case is the more likely is it to be accompanied \)j leucocytosis 
and the more numerous will be the nucleated red corpuscles, always 
more numerous here than in anaemia of adults. 

In syph'dls, hereditary or acquired, the red cells may fall below 
1,000,000 and the leucocytes may rise as high as 58,000 (Loos). 
The haemoglobin may be proportionally diminished, or may be even 
lower than the percentage of red cells, so that a ''chlorotic " condi- 
tion obtains. 

Such cases have been called chlorosis, but it seems better to con- 
fine this term to anaemia of unknown origin and favorable course 
occurring in women soon after puberty, since obviously secondary 
cases may have similar blood. 

Rickets in a case observed b}^ v. Jaksch caused a fall of the red 
cells to 750,000, and Luzet counted 1,590,000 in a similar case. 
The haemoglobin is usuall}* low, but Hock and Schlesinger found 
60 per cent with 2,300,000 red cells, a color index of 1.2-f . 

Leucocytosis may occur even when no anaemia is present. Hock 
and Schlesinger found 45,000 leucocytes in a rachitic child of six- 
teen months, sound in otlier respects and not anaemic. Acute gas- 
tritis causes at first only leucocytosis (with increased percentage of 
lymphocytes). If it becomes chronic the reduction of red cells is 
severe. Hayem found only 685,000 red cells per cubic millimetre 
in an infant of two months, though recovery eventually took place. 

In tuberculosis of the lungs and peritoneum in a child of seven, 
Monti and Berggrlin counted 3,230,000 red and 17,200 white cells 
with 52 per cent of haemoglobin. 

Qualitative Changes. 

The exaggeration characteristic of all blood changes in infancy 
extends to the presence of nucleated red corpuscles, which in all 
forms of infant's anaemia are ver}- numerous. What has been 
described on page 85 as the typical megaloblast, a large pale- 
stained nucleus in a very large cell (see Plate IV.), is relatively 
rare in infancy. The nuclei are almost always stained whatever 
their size, and apt to be small. Dividing nuclei are very common, 
both by karyolysis and karyokinesis. These changes are most often 



THE AX.EMIAS OF INFANCY. 



517 



found in the anaemias of the severest type and those which resemble 
leukajmia (see page 525), but may occur in any marked secondary 
anaemia. Polychromatophilic and " degenerative " changes are very 
common in severe cases. 

The increased leucocyte count, so frequently found, is often made 
up of a majority of lymphocytes. This change, as above said, is 
not characteristic of rickets, syphilis, or any other cause of anaemia, 
but it is to be regarded as a mark of the arrest of development or 
reversion to an earlier type of tissues brought about by various dis- 
eases in early infancy. Sometimes the large lymphocytes and some- 
times the small are in excess, and for a time the blood may simu- 
late closely that of lymphatic leukaemia, as the following cases 
illustrate. 













6 






§... 


o 

ll 


A 












Age. 


Sex. 


Red 

cells. 


White 
cells. 


11 


1. 




St 


a 

ll 


1 


o 


V . 

WO 

ll 


Remarks. 


^• 








iTjM 


s =^ 


^H >-■ 


i- >i 


^.^ 


S ^ 


o 


Sj 


s ^ 




z 










?^ 


Ph 


(^ 


Ch 


Pi 




34 


^ 
^ 


Z; 




1 


1 




1,836,000 


65,000 


13 


20.6 


78.1 




0.3 


1.1 


500 


March 13th 










78,000 




19.1 


80. 




.3 


.6 


54 




5(H) 


March 23d 










88,000 




14.3 


84. 




3 


1.6 


48 


3 


500 


March 31st 


o 


Inf. 




4,300,000 


31,000 


60 


57.5 


26. 


15.0 


.5 


1.0 


11 


89 




July 14th 
























17 


1,000 


July 19th 


3 IVs 


Male 


3,-500,000 


22,000 




** 


46.3 


7.6 


iy.2 


10.0 


31 


50 


500 


Death 



The cases in the following table (from Fowler : Brit. Jled. Jour.^ 
September 6th, 1902) are tabulated in the order of their severity. 
The splenic enlargement was present in all cases and rickets in all 
but two; but Morse has shown that similar blood changes may 
occur with no splenic enlargement (see page 522). Four of the 
patients died with bronchopneumonia, three recovered, and the re- 
sult of the rest is uncertain. 

Poikilocytosis was slight, but variations in size and in staining 
reaction were common and marked. Megaloblasts were found in 13 
of the 20 cases, but never exceeded one-quarter of the number of 
normoblasts. Contrary to the rule in the anaemia of adults, nu- 
cleated red cells are here numerous even in some of the mild cases. 
In 16 of the cases the average percentage of small lymphocytes was 
26; large lymphocytes, 21; and transition als, 12.8. "Transitional 
neiitrophiles " (see page 102) were present in all cases. 



518 SPECIAL PATHOLOGY OF THE BLOOD. 

Table CXVIL— An.kmia in Lnkants. 















1 


c 


•{. 


1 


i 


M 


5 










i 


_. 






T. 


.2 


>. 


2 


1 
1 


s. . 

•3 £ 


i 




1 




\ 




1 




? 


_§. 


\t 


i 




— ? 


a 








■=■ 














t - 


c 




r- 




t 


to 


■r- — 


c . 


c 


c % 


c 


c 












T_ 




X 


_ V. 


a> 






a; 




o 
d 




i 


a 




53 




'^t 


fe 


aj a 


% 




■^ = 


Z 


^ 


< 


O 


^ 


= . ^ JO 


c; 


C- 


cu 


c- 


^ 


'2 " 


1 


M. 


26 


February 28th.... 


1.146,(MI0 


20 


8,600 0.8 


1 to 131 


50.0 


46T 


Te 


2.2 


1,376 








March 22(1 


1,540.0(K) 


25 


8.900 .8 


1 to 175 


59.6 


34.8 


1.0 


4.6 


567 








April 2rth 


l,9(«,tMX) 


32 


8,12.5 .8 


1 to 238 


57.0 


37.0 


.2 


5.8 


1,1(X1 








May 26th 


1.525.0U) 




10,900 .... 


1 to 140 


59.6 


28.7 


1.8 


10.0 


.544 








June 16th 


2,O7.").()0(l 


'.'.'.'. 


5,900,.... 


1 to 3;-)l 


69.0 


28.0 


.8 


2 


.371 


2 


M. 


11 




2,2(JO,000 


30 


12,000; .7 


1 to m 


66.0 


31.4 


.8 


i!o 


576 


3 


F. 


16 




2,360,000 


38 


14,0(X) .6 


1 to 18:3 


68.8 


28.8 


2.0 


.4 


175 


4 


F. 


11 


February lltli 


1.156,000 




32.500 .... 


1 to 51 


















February 23d 


2,()40,(XK) 


'27" 


25.700 .6 


Ito 79 


49.0 


49.0 


"a 


1.6 


2,313 








March 2d 


2,920,(KK) 


30 


2:5.200 .5 


• 1 to 125 


















March 10th 


2.66(),(K)0 


30 


18,400 .6 


Ito 144 


61.5 


32.5 


3.0 


3.0 


1,300 








April 4th 


2,8(»0,O0U 


18 


45,00(J .3 


Ito (52 












5 


F. 


11 


February ITth 


2,640,000 




35,200 .... 


1 to 75 


















February 25th.... 


3,160,000 


o~ 


27,700, .4 


Ito 114 


62.0 


34.0 


2 


3.0 


1,600 








March 1st 


3,180.000 


30 


20.000 i .5 


1 to 159 


















March 0th 


2,600,000 


35 


22,900 .6 


1 to 112 


69.0 


28.2 


.8 


4.0 


2,770 


<6 


M. 


16 


Septeiiiher 25tli.. . 


2,6(¥).0(Xt 




22,6(X) .... 


Ito 115 


67.2 


30.4 


.4 


2.0 


790 








October 2d 


2,900.(KXJ 




21,600 .... 


1 to m 


64.0 


33.0 




3.0 


720 


7 


M. 


16 


June 3(lth 


2,.500.1KX) 





40,0a) 1 . . . . 


1 to 62 


















November 26th. . . 


3,537.000 




16,300 .... 


1 to 216 


56.0 


35.0 


7.0 


2.0 


1,5.33 








December 1st 


4.000.000 


'eo' 


21,800' .7 


1 to 181 


















December 12th... 


3,&50,{IOO 


60 


21,800 , .8 


1 to 166 


52.0 


37.2 


7.4 


2.4 


1,090 








December 29th... 


4.200,000 


68 


17,500 1 .7 


Ito 240 


















March 3d 


4,940.000 


72 


12,600 ! .8 


Ito 38:3 


58.0 


:37.0 


4.0 


1.0 


Few 


8 


M. 


13 


August 8th 


2.800.0fX» 


m 


9,800 1 .6 


Ito 286 


70.2 


2.5.5 


.3 


3.5 


466 








Novemtier 11th. .. 


3.25(>.0(XI 


38 


12,600 ! .6 


1 to 290 


6.5.0 


30.6 


.4 


4.0 


540 








January 8th 


4,800.fHH) 




10,100 .... 


1 to 4m 


56.0 


42.4 


1.0 


.6 


126 








February 13th .... 


4.216.000 


.58 


9.800 .7 


Ito 430 


















March 24th 


3.8S(i.nii;i 




11. (HK) .... 


1 to a52 


















June 24tli 


;)!.-)l(U)iiii 


5s 


6.3(10 ' .8 


1 to 557 


52.6 


42.4 


.4 


4.6 


327 


9 


f. 


24 

10 




2 370.00(1 


'45' 


5,800 .... 
17,000 1 .7 


1 to 408 
1 to 182 


47.2 

63.0 


51.0 
a5.8 


.8 
.5 


1.0 
l.O 


150 


10 


March 2rth. !.'.'.'!! 


3.100.(X10 


1,700 








January 15th 


4,800.t)00 


70 


10,100' ,8 


1 to 475 


51.2 


48.0 


.8 




40 


11 


F. 


11 




3,452,000 


35 


23,900 1 .5 


Ito 144 


38.0 


59.0 


1.2 


1.8 


1,300 


12 


M. 


18 




3,800,000 


46 


a5,200i .6 


1 to 108 


38.3 


.59.0 


.2 


2.5 


905 


13 


F. 


15 


May 36th!! ....... 


3,960.000 


57 
47 


27,000 .7 
19,600! .6 


1 to 146 
1 to 174 


&5.0 

58.8 


30.0 
38.0 


is 

1.0 


4.5 

2.4 


964 




June 16th 


3.410.000 


1,460 


14 


M. 


15 




4.(X10.000 


66 


19.600 ' .8 


1 to 200 


54.6 


44.2 


.6 


.6 


138 


15 


K. 


26 




4.(KX).000 




12,000 .... 


1 to a33 


56.0 


34.0 


2.0 


8.0 


1,340 


16 


F. 
F. 


13 




4,100,000 
4,160.000 


'56' 
60 


12,800 1 .6 
11,860 .7 


1 to ;320 
1 to 330 


61.0 
61.2 


36.5 
36.2 


1.5 

1.4 


1.0 

.8 


20 


17 




512 


18 


F. 


18 




4.900,000 


80 


10,500 


.8 


Ito 446 


55.8 


43.8 


.4 




30 


19 


F. 


18 


.'.■;;;;;::.■.■.■■.;■.■..; 


4,940,000 


65 


10,266 


.6 


1 to 49(i 


62.8 


35.4 


1.6 


"0 


20 


20 


M. 


13 




5,020,000 


70 


15,300 




Ito 330 
Average 


57.0 
.59.1 


40.0 
36.9 


2.0 
1.2 


lio 


612 



A further qualitative change already alluded to (see page 
111) is the occurrence of myelocytes. We have seen that small 
percentages of these cells are not uncomnionl}^ seen in the anaemias 
of adults. Now this, like all other blood changes, is exaggerated 
ill infanc}^ Myelocytes are more apt to appear and in greater num- 
bers. Their presence is not characteristic of any one disease, but 
they are commonest in the severer tjq^tes of secondary anaemia, such 
as those following sj'philis and rickets. Their significance is about 



ANEMIA INFANTUM PSEUDOLEUK^MICA. " 519 

the same as that of normoblasts/ At times, however, they are so 
numerous as to make us hesitate somewhat before we exclude splenie- 
myelogenous leukaemia. 

This brings us naturally to the discussion of the difficulty of dis- 
tlngidshing the different hlood diseases in infancy, which naturally 
centres in the question of the existence and nature of the so-called 

"ANEMIA INFANTUM PSEUDOLEUK^MICA." 

Von Jaksch's ' description of this disease (which he was the first 
to recognize) includes the following elements : 

1. Grave anemia— e.<7., 820,000 red cells per cubic millimetre 
in one case. 

2. Extensive leucocytosis— e.^., 54,660 white cells per cubic mil- 
limetre, in the same case. 

3. Great variations in the form, size, and staining of the white 
cells. 

4. Deformed, degenerated, and nucleated red cells. 

This description was given by v. Jaksch^ in 1889. He stated 
the relation of white to red corpuscles as 1 : 12, 1 : 17, and 1 : 20 in 
the cases seen by him. Later he reported three cases in one of 
which the white cells numbered 114,150 and the red 1,380,000. 

The differential counts are not carefully given. 

Almost at the same time Hayem '^ reported a similar case, and 
noted the abundance of nucleated red corpuscles many of which 
were undergoing mitosis. This w^as verified by Luzet," who re- 
ported two cases in May, 1891 (A7rh. gen. de Med.)] but although 
Luzet continues to use the name suggested by v, Jaksch, he de- 
scribes the disease so differently that it is difficult to see why the 
same title should be given to it. He agrees with v. Jaksch in 
thinking that it is not simply a severe secondary anaemia due to 
syphilis, rickets, tuberculosis, or infectious disease. 

Somewhat similar cases had already been described by various 

^Weil and Clerc (Rev. Mens. d. Mai. a I'Enfance, No. xxi., 1902) have 
put together a number of cases from their own and others' experience, show- 
ing that splenic enlargement and myelocytes in the blood are of frequent 
occurrence in the anaemias of infancy. They attempt quite unsuccessfully to 
build up from these data a new clinical entity. 

2 Von Jaksch: Wien. klin. Woch., 1889, Nos. 22, 23. 

3 Hayem: Gaz. des Hopitaux, 1889, No. 30. 

4 Luzet: Diss., Paris, 1891. 



520 5PECIAL PATHOLOGY OF THE BLOOD. 

Italian writers (e.y., Fede) under the title of ^' Infectice Splenic 
Anmmia of Infants. ^^ Baginsky,' Senator,- Fischl/ Andeoud/ Monti 
and Berggrlln/ Felsenthal/ Kaudnitz/ Epstein/ Alt and Weiss/ 
Hock and Sclilesinger/" Crocq/' and Rotch/^ have written upon the 
subject, and hardly any two have described the same set of facts or 
agreed as to the meaning of the term. 

The chief importance of the heterogeneous group of cases which 
have received the name of anosmia Infantum pseudoleukcemica ^qqiws 
to me to be as a proof of the difficulty of distinguishing the various 
blood diseases in infancy. Among the cases reported under this 
name are some which might be any one of the following list : Per- 
nicious anaemia, secondary anaemia witli leucocytosis, Hodgkin's 
disease, lymphatic leukaemia, and probably splenic-myelogenous 
leukaemia. 

{a) Kotch and Ladd " have reported a case occurring in an in- 
fant ten months old in which the blood had all the characteristics of 
pernicious anaemia as seen in adults, except that the color index was 
never high. I examined the blood and predicted the baby would 
die. It rapidly recovered and has now been well for two years. I 
know of no case precisely similar. ]N[ost of the few reported cases 
of pernicious anaemia in infancy have shown moderate leucocytosis 
(as compared with adult blood), a fact which deprives us of one of 
the means of distinguishing the disease from secondary anaemia. 
The reports as to nucleated corpuscles very rarely separate normo- 
blasts from megaloblasts, and we have no way, therefore, of being 
sure on this important point. The liigh color index and large di- 
ameter of the red cells are oocasionally seen in other anaemias of 
infancy and are not always present in pernicious cases. The great 
fatalit}' of all kinds of anaemia in infancy prevents our calling a 
case 2)ernlcious because of a fatal termination. Enlargements of the 

^Baginsky: Arch. f. Kinderheilk., 1892, vol. xiii. 

■^Senator: Berlin, klin. Wocli., 1892. ^Fiscbl: Loc. cit. 

^ Andeoud: Rev. med. de la Suisse rom., 1894, p. oOT. 

^ Monti and Berggriin : Loc. cit. ^ Felsenthal : Loc. cit. 

''Rudnitz: Prag. med. Woch., 1894, p. 6. 

^Epstein: Prag. med. Woch., 1894, p. 6. 

9 Alt and Weiss : Centralbl. f. med. Wissenschaft, 1892. 

'^Hock and Schlesinger: Loc. cit. 

^^ Crocq: "fitude sur I'Adenie," etc., Brussels, 1819 (Lamartin). 

^■2 Botch : Paediatrics, 1895, p. 361. 

^^ Botch and Ladd: Paediatrics, September, 1901. 



"an.^mia infantum pseudoleukjemica. " 521 

liver and spleen occur in many cases of each type of infantile anse- 
niia, and occasionally in pernicious anaemia of adults. They do not, 
therefore, exclude pernicious ansemia in infancy. 

Bearing these facts in mind, it is evident that some of Luzet's 
cases of " anaemia infantum pseudoleukaemica " may have been per- 
nicious anaemia. Von Jaksch's own cases may have been either («) 
Hodgkin's disease with leucocytosis, (b) grave secondary anaemia 
with leucocytosis (Monti and Berggrtin), or (c) leukaemia. 

(b) Hodgkin's disease, which v. Limbeck finds to be very com- 
mon in infancy, may affect the liver and spleen and not the exter- 
nal lymph glands, and may be accompanied by anaemia and leuco- 
cytosis such as V. Jaksch describes. Epstein considers that this is 
the case, and hence denies the existence of any such disease as the 
anaemia infantum pseudoleukaemica. 

(c) As any anaemia secondary to rickets or syphilis may or may 
not have enlarged spleen and liver and marked leucocytosis, Ave can- 
not tell from v. Jaksch's description that we are not dealing in his 
cases with secondary anaemia. The table on pages 522 and 523 
from Morse ^ gives a fair sample of cases of anaemia in infancy of 
various degrees of severity, and shows the lack of any interdepend- 
ence between splenic tumor, the number of leucocytes of erythro- 
cytes or of megaloblasts, and the prognosis. 

(tZ) Since v. Jaksch does not give any accurate differential count 
of the leucocytes, there may have been large numbers of myelocytes 
in his cases for all w^e know, or an overwhelming percentage of lym- 
phocytes, i.e., either type of leukaemia. 

One of the cases reported by Kotch as " anaemia infantum pseu- 
doleukaemica " had 80 per cent of lymphocytes in a leucocyte count 
of 116,500, the ratio of white to red cells being 1: 11, and the nu- 
cleated corpuscles abundant. The external lymph glands as well 
as the liver and spleen were enlarged. How such a case is to be 
distinguished from lymphatic leukaemia without autopsy I cannot 
see. Large numbers of nucleated corpuscles with mitoses (present 
in this case) are to be found in any anaemia of infancy in which the 
red cells, as in this case, have sunk as low as 1,311,500, and there- 
fore do not exclude leukaemia. 

Von Jaksch protests that his cases are not secondary to rickets 
or any other disease, but Fischl ' in a careful study of all the pub^ 

1 Morse: Boston Med. and Surg. Jour., May 28tli, 1903. 
•2 Fischl: Zeit. f. Heilkunde, 1892. 



522 



SPECIAL PATHOLOGY OF THE BLOOD. 







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524 SPECIAL PATHOLOGY OF THE BLOOD. 

lishecl cases finds that out of a total of eighteen cases sixteen had 
severe rickets and two hereditary syj^hilis. 

The writings of Kaudnitz, Ebstein, Felsenthal, Fischl, and v. 
Limbeck, which deny the separate existence of the anseniia infan- 
tum pseudoleuksemica, are convincing to me, and are reinforced by 
the few cases of bad anaemia in chiklren which I have seen. We 
must try to distribute the cases of anaemia with leucocytosis and 
large spleen under pernicious anaemia, secondary anaemia, and leu- 
kaemia. But our problem is not yet nearly solved. All we have 
gained is the belief that v. Jaksch's new disease does not help us 
to classify these doubtful cases. The difficulty is still very great. 
The following cases, reported hy Dr. Vickery in the Medical Xeus 
for December, 1897, illustrate this: 

Case I. — A male child of sixteen months with symptoms of 
grave anaemia, greatly enlarged spleen and slightly enlarged liver, 
showed the following figures : Red cells, 2,500,000; white cells, 
22,000. Differential count of 500 cells showed : Lympliocytes, 53.8 
per cent (46.2 of the smaller type); polymorphonuclear cells, 29.4 
per cent; eosinophiles, 6.2 per cent; nn'elocytes, 10 per cent. 

While counting these, 147 nucleated red corpuscles were seen, 
of which 21 were normoblasts, 50 megaloblasts, and 47 microblasts; 
6 showed mitosis in their nuclei. 

The child died shortly after without any complication or inter- 
current disease. No autopsy. Xo evidence of rickets or syphilis 
or other previous disease. 

Case II. — Young infant with enlarged external lymph glands 
and very large spleen. July 14th, 1897— Eed cells, 4,300,000: 
white cells, 31,000; haemoglobin, 60 per cent; polymorphonuclear 
neutrophiles, 57.5 per cent; small lymphocytes, 26 per cent; large 
Ijanphocytes, 15 per cent; eosinophiles, 0.5 per cent; myelocytes, 
1 per cent. 

One or two nucleated red corpuscles in every field. Out of 100 
of them 89 were large and 11 small. ]Mam^ showed mitosis. Poly- 
chromatophilic forms numerous. July 19th — Seveuten megalo- 
blasts seen while counting 1,000 white cells. Blood is otherwise 
about the same. The case was lost sight of and not traced. 

Xow I see no reason for supposing these cases to represent a 
new type of disease, and yet I cannot feel perfectly safe in classify- 
ing them as primary anaemia, secondary anaemia, or leukaemia. 

(a) Primary or pernicious anaemia should have a lower count of 
red cells. The percentage of myelocytes in the first case (10 per 
cent) is higher than in any other case of pernicious anaemia on 



"ax.emia infantum pseudoleuk^mica." 525 

record, though in one adult case with autopsy I found 9.2 per cent 
with a leucocytosis of 12,500, or 1,150 myelocytes per cubic milli- 
metre, against 2,200 per cubic millimetre in this case. 

(b) It is hard to call an anaemia secondarj^ which kills with no 
complications and when there is no evidence of any disease of which 
it can be secondary. 

(c) For splenic myelogenous leukaemia the total leucocyte count 
and the percentage of myelocytes are very small in either case. 
Still the leucocyte count may drop very low in leukaemia even with- 
out any inflammatory complication. Such a case is reported by 
Osier, in which the leucocytes fell to 7,500, of which only 300, or 
four per cent, were myelocytes. 

Hayem (loc. clt., p. 864) in a ten-months-old child counted 
2,712,500 red and 33,000 white cells, almost the same figures as in 
the case just quoted.. [Ha^'em unfortunately gives no differential 
count, but apparently considers the case leukaemic because of the 
enormous number of nucleated red cells, many with mitoses.] 
Morse's case of leukaemia in infancy had 2,900,000 red and 48,000 
white cells. Twenty-one and four- tenths per cent of the leuco- 
cytes, or about 10,000, were myelocytes. The same abundance 
of nucleated red cells (some with mitoses) were here present as in 
Hayem's case, so that there is evidently nothing peculiar in their 
presence in the disease described by v. Jaksch, as Luzet supposed. 

These cases show that leukaemia may at certain periods present 
just such a blood picture as was present in the above-quoted case, 
and that the number of leucocytes in the leukaemia of infants may 
be no greater than that in any anaemia with the leucocytosis so com- 
mon in children. It seems to me the most natural conclusion to be 
deduced from these facts is that we meet with cases in infancj 
tchich are apparently intermediate between leukcemia and p)ernicious 
anwniia. I have pointed out elsewhere that there are many points 
of resemblance between the two diseases. The case of leukaemia 
reported by Osier showed at one period— the period of remission— 
a fall in the number of leucocytes and in the percentage of myelo- 
cytes till the blood was practically that of pernicious anaemia. 

Dr. Eotch-'s case (above quoted) is another in which the diagno- 
sis seems to lie somewhere intermediate between the two diseases, 
anaemia and leukaemia. The case which I have quoted above seems 
to me on the whole nearer to the type of pernicious anaemia than of 
leukaemia, and Dr. Eotch's nearer to the latter than to the former; 



526 SPECIAL PATHOLOGY OF THE BLOOD. 

but each is really intermediate, so far as the blood goes, between the 
two diseases. 1 have no intention of. suggesting that the organic 
lesions in these cases are intermediate between leukaemia and jjer- 
nicious anaemia. It is simply the blood that is so. 

Engel's case, reported in Virchow's Archiv, vol. 135, suggests 
the same thing. He calls the case one of ^^ p^eudo-pernicums <iiuv- 
mia.^^ Myelocytes were abundant. 

Pobjmorphous Condition . 
This illustrates that "polymorphous" condition of the blood 
which V. Jaksch supposed to be characteristic of the anaemia infan- 
tum pseudoleukaemica. The same thing was ver}^ marked in all the 
bad cases of anaemia Avhich I have seen, including the case above 
mentioned, and a case of true leukaemia in a girl of eight. The im- 
pression one gets from the field of a stained specimen is that no two 
ichite coipuscles are alike. Every species is subdivided into several 
sub- varieties and all stages of degeneration are to be seen in each 
variety. But this is characteristic of any very severe infantile anae- 
mia and not of any single type. 

LEUKEMIA. 

In Morse's careful article of August, 1894 (Boston Med. and 
Surg. Journal), twenty cases of leukaemia in infancy are collected. 
As he rightly says, probably most of these cases were not genuine. 
Only one of them includes a differential count, and this is in a lym- 
phatic case. ^Morse's case was at that time the only one of the 
splenic-myelogenous type on record in which the diagnosis is made 
reasonably certain by a color analysis. Fischl in 1892 said that 
there was no case on record with a differential count. 

A case was seen in 1890 by Dr. F. C. Shattuck, which was ap- 
parently acute, the symptoms appearing only six weeks before 
death, (^over-glass preparations examined by W. S. Thayer showed 
a ratio of about 1 white to 20 red cells. The differential count ' 
showed: Small lymphocytes, 97.9 per cent; large lymphocytes, 
0.7 per cent; polynuclear cells, 1.4 per cent; eosinophiles, 0.08 per 
cent. 

The other case reported by Morse has been mentioned above. 

Charon and Giratea ^ have recently reported a case in a child of 

^ Reported by Thayer in the Boston Medical and Surgical Journal, 1893, 
vol. cxxviii., p. 183. 

•^Bull. d. Soc. Roy. d. Sciences Med., etc., Bruxelles, 1897, No. 7. 



LEUKEMIA. 



527 



eight with 880,000 red cells, 305,000 white cells, aud 39 per cent 
of haemoglobin. It was apparently of the myelocyte type. E. 
Miiller thinks that there are about five other (German) cases on 
record, all of acute leukaemia and all with a similar blood count, 
though in some the large lymphocytes (without neutrophilic gran- 
ules) have been described as "myelocytes." 

Miiller ' has reported with great care three cases of leukaemia, 
all of them in boys four years old— all apparently acute and of the 
gastro-intestinal type— i.e., the glands and follicles throughout the 
whole length of the alimentary tract being the chief seats of infil- 
tration, though the liver and spleen were also enlarged. The counts 
were as follows : 





Case I. 


Cask II. 






April 
30th. 


May 1st. May 2d. 


May 3d. 

1.232,000 

6,800 

Death. 


CiSE in. 


Red cells 


1,508.000 
109,500 
40% 


1,684,000 1,362.000 
93,800 46,000 


2,290.000 
206,000 
25^ 


1.308,000 
420,000 


White cells 


Hsemoglobin 






Polymorphonuc 1 e a r 

neutrophiles 

Small lymphccytes2.. 
Large lymphocytes . . 
Eosinophiles 


2% 

85% (8-10 fj. diameter). 

13^ 


Many. 

Few. 
Few. j 
Many. ! 


1% 
15^ 
84$« 


.7 
2. 

97.3 
.01 






1 


Normoblasts 


Few. 
Few. 


Two n r m - 
blasts seen in 
counting 
1,135 1 e u - 
cncytes. 


Seven seen in 




counting 1,118 










leucocytes. 



Since these reports a considerable number of cases of lymjihatic 
leukaemia in infancy have been published — some of them acute and 
not differing markedly from those which occur in adults. Myeloge- 
nous or mixed-cell leukaemia appears to be rare in infancy. Only 
a few cases are on record so far as I am aware. 

1 Jahrbuch ftir Kinderheilk., 1896, vol. xliii. 
'^ All with large pale nuclei. 



PART VII. 

EXAMINATION OF THE SERUM. 



CHAPTER XV. 



Ix a summary of recent literature on serum reactions — a sum- 
mary which is a model of concise and lucid statement — Sailer ^ 
has distinguished fourteen types of serum reaction, under each of 
which numerous sub- types can be recognized. Sailer's list is as 
follows: 



1. Reactions between tlie 
micro-organisms producing 
infection and the serum of ! 
tiie infected subject (e.g., be- 
tween typhoid bacilH and 
typhoid serum). 

2. Reactions between the | 
.(J corpuscles of some ani- 
mal and the serum of an 
animal protected specificalh' 
against them (naturally or 
artificially). 

3. Reactions between the "] 
normal serum of various ani- j 
mals and different species of i 
micro-organisms. J 



1. Agglutination (Widal's reaction). 

2. Solution or lysis (Pfeiffer's phenomenon). 

3. Formation of long skeins of tangled ba- 

cilli. 

4. Formation of a precipitate in germ-free, 

filtered cultures on addition of the cor- 
responding serum. 

5. Agglutination (clumping). 

6. Solution (hcemolysis). 

7. Formation of a precipitate when the sera 

of the two animals (the attacking and 
the attacked) are mixed. 



8. Agglutination (clumping). 

9. Solution (lysis). 



4. Reactions between the ] 10. Solution (autolysis, isolysis, and hetero- 

normal or patliological serum I lysis). 

of some animal and the red )■ 1\. Agglutination (rouleaux formation is 

corpuscles of the same or some I probably a variety of auto-agglutina- 

other animal. J tion). 



Sailer: Univ. of Penn. Med. Bull.. August to September, 1903. 



THE WIDAL REACTION IN TYPHOID FEVER. 529 

5. Reactions between some ^ 
species of hody cell (liver I ^^ Agglutination, 
cells, leucocytes, spermato- I 10 a i ^- ,x. ^ ^. - ^ 1 • 

\^r.\ cIa +V^ o^^^ ^f \^^' Solution (hepatolysis, leucolysis, sperma- 

tolysis, etc.). 



zoa, etc.) and the sera of 
animals immunized against 
that cell. 



6. Reactions between red 
cells and bacterial cultures. 



14. Solution. 



To these might be added the reactions between cellular prod- 
ucts, such as milk or Q^'g albumen, and the serum of an animal 
"immunized" against them (i.e., previously injected with milk or 
Qg'g albumen). 

Any attempt to discuss these topics (which are I think the most 
vitally interesting and important in medicine to-day) would lead far 
beyond the limits of this book, But it is well, I think, to note that 
the particular types of serum reaction which we use in diagnosis 
to-day (the first two of the above list) have their place among a 
number of other types of serum reactions, any of which may in the 
near future become of value in clinical diagnosis. 

THE WIDAL REACTION IN TYPHOID FEVER. 

General Description. 

Although the phenomenon of agglutination is to be obtained in 
various infections, natural as well as experimental, and with vari- 
ous cells and body fluids, I shall describe as a typical case of it the 
reaction which may take place when the serum of a patient ill with 
typhoid fever is added in certain proportions {vide infra) to a young 
bouillon culture of well-certified and virulent typhoid bacilli. In a 
drop of such a mixture, examined between slide and cover glass ' 
with a magnification of 300 diameters or more, we notice at once or 
within thirty minutes a marked slowing of the progressive move- 
ments of the bacilli or an unequal distribution of them in the differ- 
ent parts of the preparation. Whichever of these changes occur 
first, the slowing of locomotion or the tendency to grouping, the 
other soon follows, and then both processes go on together, as ad- 
mirably described by Biggs and Park : '' 

1 Hanging-drop preparations are often recommended, but a simple slide 
and cover glacs are as good for the purposes of this reaction. 

2 American Journal of the Medical Sciences, March, 1897. 

34 



530 



SPECIAL PATHOLOGY OF THE BLOOD. 



" Some of the bacilli soon cease all progressive movement, and 
it will be seen that they are gathering together in small groups of 
two or more, the individual bacilli being still somewhat separated 
from each other Gradually they close up the spaces between them 
and clumps are formed According to the completeness of the re- 
action, either all the bacilli may finally become clumped and im- 



FiG. 47.— Pure Culture. 





Fig. 48.— Fartial Reaction. 



Fig. 49.— Typical Clumping. 



mobolized or only a small portion of them, the rest remaining 
freely motile, and even those clumped may appear to be struggling 
for freedom. With blood containing a large amount of the aggluti- 
nating substances all gradations in the intensity of the reaction may 
be observed, from those shown in a marked and immediate reaction 
to those appearing in a late and indefinite one, by simply varying 
the proportion of blood added to the culture fluid " (see Figs. 47, 48, 
and 49). 



THE WIDAL REACTION IN TYPHOID FEVER. 531 

The groups or clumps above described constitute the important 
part of the reaction for diagnostic purposes. Of the loss of motility 
more will be said later. 

Techxique or the Clump Eeactiox ix Typhoid Fever. 

Our account of the methods of obtaining the clump reaction may 
be divided into the following parts: 

1. The body fluids to be used and the methods of obtaining 
them. 

2. The cultures. 

3. Dilution and the time limit. 

1. The Body Fluids to be Used. 

■ Experiments have proved that the reaction can be obtained with 
the following fluids : 

(a) The whole blood, fluid or dried.- 

(b) The plasma and serum, fluid or dried. 

(c) Also blister fluid, the fluid contents of normal serous cavi- 
ties, breast inilk, pus, tears, and other body fluids. 

Of all these fluids, the blood, or the serum, fresh or dried blis- 
ters are the only ones used in clinical work, 

1. Use of the Whole Blood — Fluid 

The advantages of this method are (a) its quickness, and (It) 
the small amount of blood (one drop) sufiicient for the test. 

I have used this method in most of my cases and always found 
it satisfactory and convenient. 

Procedure. — Suck up some water with a medicine-dropper and 
expel ten drops of it into a watch glass. Then empty and dry the 
dropper, draw up from the watch glass the ten drops just expelled, 
and mark with a file on the side of the dropper the point up to 
which the ten- drop column extends. Mark also the point to which 
one drop (expelled and then sucked up again as before) will rise. 

Ten drops of the bouillon culture of the bacilli to be used are 
then expelled into each of several small test tubes, and one of these 
tubes is carried to the bedside. After pricking the ear as if for 
blood examination' (see page 7), put the end of the medicine-drop- 

= Squeezing and milking the ear are of no harm in t)iis procedure and enable, 
us to get on with a tritiing and painless puncture. 



532 SPECIAL PATHOLOGY OF THE BLOOD. 

per into the blood drop, and carefully draw back the rubber bulb 
(which has been previously pushed down over the glass part of the 
dropper) until the blood rises to the mark for one drop. Wipe from 
the outside of the dropper any blood that may adhere there and 
then expel the drop into one of the little test tubes containing the 
ten drops of bouillon culture. In this way blood can be taken for 
examination from a dozen patients in as many minutes. 



2. JVhole Blood— Dried. 

The advantages of the method are (a) the ease and quickness 
with which the blood can be obtained, (b) the convenience for trans- 
portation by mail, and (c) that it does not deteriorate or become 
contaminated by bacterial growth, as specimens of fluid blood or 
serum are so apt to do. Its clumping power is fully equal to that 
of the serum in most cases. ^ 

Procedure. — The blood should be dried either upon a glass slide 
or on a piece of glazed paper or card. Any absorbent substance is 
less available. Glass is easier to sterilize than paper. Several 
large drops should be placed in different parts of the glass or paper 
and thoroughly dried. 

If paper lias been used, we cut out the dried blood drop with a 
pair of scissors, keeping close to the blood all round, and drop it 
into a test tube containing one or two drops of water, in which 
with some sharp-pointed instrument we mix the dried blood, free- 
ing it as well as possible from the paper. 

To the liquid so obtained add eight or nine drops of the bouil- 
lon culture of bacilli and proceed in the ordinary way. Or we may 
drop the fragment of paper holding the blood directly- into ten drops 
of bouillon culture — using the bouillon itself to soak off the blood 
from the paper. - 

' Widal and Delepine think the fluid serum is slightly more powerful than 
the dried blood. Johnson admits that in one-tenth of the cases the serum is 
the more powerful. I have obtained reactions with the dried blood in only 
;seveD-eighths of tlie cases in which I got them with the fluid serum. 

- Some observers gather the blood on a bit of tinfoil and later crack it off, 
and after weighing it can make exact dilutions. Or we may soak blood into 
hits of filter paper of standard size and porosity and thus acquire a known 
amount as a basis for exact dilutions. 



THE WIDAL REACTION IN TYPHOID FEVER. 533 

The Fluid Serum, 

The ear is pricked in the ordinary way and about twenty drops 
are forced out by strong squeezing. The blood is received in a 
small (preferably two-inch) test tube. 

The blood when collected may be at once centrifugalized, and 
the plasma used for the test, or we may wait till clotting occurs and 
use the serum. When blood is collected in test tubes, it is conve- 
nient to free the edges of the clot from the tube all round with some 
sharp instrument, so that the serum may not be pinned down under- 
neath the clot, as it often is. If this is done, a drop of serum can 
be had within two or three minutes, and is then mixed with ten 
drops of bouillon culture, as above described, and examined at once 
between slide and cover glass. 

(Dried serum can be used in the same way as dried blood, but 
has no special advantages and has not been frequently employed by 
any observer.) 

2. The Cultures of Typhoid Bacilli to be Used. 

1. The stock cultures grow best on agar at room temperature. 

2. Ordinary peptone bouillon, free from sediment, is the best 
medium for the test culture. lb should be just on the verge of lit- 
mus acidity, giving no blue to the red paper and requiring 3 5 per 
cent of normal alkali to render it neutral to phenolphthalein. 

3. The cultures should be young — that is, the transplantation to 
bouillon should have taken place not more than from twelve to 
twenty -four hours before the culture is used. 

4. The virulence and motility of the culture are very important. 
Most observers agree that the more virulent the culture the more 
readily and characteristically it is clumped by typhoid serum. 
Biggs and Park noticed that one culture of peculiarly great virulence 
recently received from Pfeiffer of Berlin worked much better in 
their cases than any other of the cultures used. 

Cultures fresh from an autopsy usually show furious motility, 
the bacilli darting about like a swarm of insects, but after repeated 
transplantations and long sojourn in the thermostat a good deal of 
this motility is gradually lost. Cultures kept at room teiiqjerature 
preserve their motility for much longer jyeriods. 

For those who have no opportunity to test the virulence of or- 
ganisms on animals, the motility is the best guide to virulence, and 



534 SPECIAL PATHOLOGY OF THE BLOOD. 

the rule should be: Amomj the ava'dahle cultures select that harlng 
the most rapid mot'ditij. 

4. Certain cultures contain small clumps of bacilli before any 
serum has been added to them. This is a very important point and 
has doubtless misled many. In consequence of this possibility 
every culture must be examined each time that a test is made. 

It is hardly necessary to say that the cultures used must have 
been submitted to all the regular tests for the recognition of tlie 
typhoid bacillus, and that the greatest care must be used to avoid 
their contamination. 

The Use of Suspensions or Emulsions of the Bacilli instead of 

Cultures. 

A few observers — particularh* Durham and Griiber — have pre- 
ferred to use a mixture of small bits of solid agar culture and bouil- 
lon instead of bouillon cultures. The majority of writers prefer 
cultures. 

The Use rf Attenuated Cultures. 

Johnson found that with his methods of technique (dried blood 
and no definite dilution) pseudo-reactions were not uncommon with 
the blood of healthy people. 

He avoids this by using attenuated cultures — i.e., old stock agar 
cultures kept at room temperature and not transplanted more than 
once a month, from which he planted his bouillon cultures. This 
gives a bacillus of reduced virulence and slow, gliding motion, which 
is clumped far less readily than the virulent varieties. Bouillon 
cultures of this kind from twelve to twenty-four hours old he found 
to react in fifteen minutes with all typhoid sera and not with other 
sera even after forty-eight hours' waiting. 

3. Dilution axd the Time Limit. 

1. Dilution. 

I have mentioned without explanation in various parts of this 
chapter that the blood serum or other fluids used must be diluted 
with at least ten times their volume of bouillon culture before any 
observation is made as to their action on the bacilli of typhoid fever. 
The reasons for this dilution and for the proportions 1: 10 are 
the following: 



THE WIDAL REACTION IN TYPHOID FEVER. 535 

It has been found, as mentioned above, that the mere formation 
pf clumps in bouillon cultures of Eberth"s bacilli is not a power ex- 
clusively possessed b}- typhoid serum. The serum of persons suffer- 
ing from other diseases and even of healthy persons will form 
clumps -exactly like those formed by typhoid h^iCilli, 2')rovided it is 
not diluted. The only known peculiarity of the typhoid serum is 
that its clumping power is (jreaft^r than that of other diseases, and 
persists in spite of dilution, Avhile the sera of diseases other than 
typhoid lose their power to clump typhoid bacilli when diluted ten 
times or more. 

2. Time Limit. 

But even this statement must be further limited. The sera of 
various other diseases, and of healthy persons, will sometimes 
clump typhoid bacilli even in a 1 : 10 dilution^ xjvovided ive give them 
time enough. We must therefore limit the period within which a 
serum must ''come up to the scratch '* and do its work, if it is to be 
considered a typhoid serum. 

Following Griiber and Durham, a time limit of one-half hour 
has been adopted by Grimbatim, Pdock, Haedke, Park, and others, 
but later research convinces me that a fifteen-minute time limit is 
safer. 

All that these more or less arbitrary hgttres stand for is this : 
that hitherto no one has rej^jorted any considerable number of cases in 
which the serum of any disease or of healthy 2^ er sons has clumj^ed ty- 
jjhoid bacilli within fifteen minutes^ when diluted 1 : 10 and used with 
unimpeachable technvjue. 

Microscop icol Exam ination. 

An artificial light is preferable. The use of hanging-drop prepa- 
rations is unnecessary, as a simple slide with a cover glass is satis- 
factory. A hanging-drop cell may be extemporized by cementing 
witli marine glue a small brass curtain ring to a slide, and inverting 
the cover glass within it, as advised by Stokes. 

I have collected over 8,000 cases of supposed typhoid fever in 
which the clump reaction was tested as above described either with 
the fltiid or dried blood. Of these, 95 per cent showed a serum re- 
action at some time in their course; 2,500 odd controls sliowed 
abottt 2 per cent of positive results in cases other than tyi)lioid. 
Altogether then about 10,500 cases have been tested. If we leave 



536 SPECIAL PATHOLOGY OF THE BLOOD. 

out the Teports of those whose experience covers less than 100 cases, 
we have left 4,339 cases observed by 18 physicians in which the 
percentage of error is 2 per cent only. 

A, C. Abbott ' reports on 11,825 cases with if not over five per 
cent between the laboratory and the clinical diagnosis. He uses 
dried blood. 

How early does the reaction appear? Few of the many observ- 
ers who have written on this point have discussed how the begin- 
ning of the disease is settled and what they mean, e.g., by the 
"fifth day of the disease." It might be dated from the first day 
of malaise and indisposition, from the nose-bleed or the beginning 
of headache, or from the time of going to bed. 

Allowing for such serious uncertainties as this, we find that 
while the majority of observers record the sixth to eighth day as 
the earliest on which the reaction appears, there are quite a number 
of cases mentioned in which it was seen on the fourth or fifth day; 
a few record reactions present on the third day, and two or three 
on the second day. 

How late in the disease does the reaction last ? The majority of 
observations agree that in mild cases the reaction may die out even 
before the end of the fever. On the other hand, the reaction usu- 
ally lasts several months, and Widal found it still present after 
one year in three out of twenty-two cases in which he ti'ied it. 
These three subjects had had very severe cases of typhoid three, 
seven, and nine years previously. It has been reported present 
twenty and even thirty years after the fever. 

The reaction almost always persists in relapses, even to a second 
or third relapse, and occasionally it is present only in relapse and 
not in the original attack at all. Biggs and Park record a case in 
which the diagnosis was proved during the original attack by punc- 
ture of the spleen, which showed a pure culture of Ebei-th's bacilli, 
yet no serum reaction was present until the second day of the re- 
lapse. I have observed several similar cases, and quite frequently 
not found the reaction until convalescence. The failure to follow 
up such cases as these accounts for many negative reports. 

The Intensity of Reaction. 

Widal and Sicard record clumping with a dilution of 1: 12,000 
and 1: 1,800 and consider that in the active stages of the disease 
' Abbott: Phil. Health Board Rep., 1899, 1900, 1901. 



THE WIDAL REACTION IN TYPHOID FEVER, 537 

a dilution of 1: 60 or 1: 80 does not usually present the reaction, 
while in convalescence the power of the serum falls off gradually 
and is not always present even at 1 : 10. 

Biggs and Park find one-half their typhoid cases furnish serum 
with the power to clump in 1 : 40 dilution by the end of the first 
week, and have occasionally noted the reaction even with a dilution 
of 1:200. 

Control Cases. 

Out of over three thousand cases of various diseases not typhoid, 
not over a dozen have been proved to clump typhoid bacilli with 
proper technique. It is quite possible that further improvements 
in technique may enable us to prevent even this very small error. 

Summary of Clinical Evidence on the Sero- Diagnosis of Typhoid 

Fever. 

The blood of over ninety-five per cent of all cases of typhoid 
shows a clumping power in some part of their course, but in at least 
half the cases this does not appear until the second week of the dis- 
ease, while in a small number of cases it first appears in relapse or 
convalescence. The clumping power may disappear before the de- 
fervescence and may be present only eight days in all; as a rule it 
persists from the sixth or eighth day until convalescence is estab- 
lished. 

In diseases other than typhoid a clump reaction is very rarely 
to be obtained, provided a dilution of at least 1: 10 is used with a 
time limit of one-half hour. There is no one disease in which 
clumping is especially apt to occur. 

Clinically the reaction is of considerable value, especially when 
the diagnosis is in doubt after the first week of the disease. 

Seeo-Diagxosis of Diseases Other than Typhoid. 
1. Cholera. 

Griiber and Durham first showed that human cholera serum 
would clump cholera vibrios, following the researches of Pfeiffer in 
vivo by demonstrating a similar reaction in vitro. 

Achard and Bensaude have applied this to the actual diagnosis 
of cholera in man with considerable success. In fourteen cases, 
thirteen clumped readily; two of these were on the first day of the 



538 SPECIAL PATHOLOGY OF THE BLOOD. 

disease.' Thirty control eases were negative. The presence of the 
pellicle renders it unsafe to use bouillon cultures except such as 
have no pellicle, for bits of it are much like true clumps. Suspen- 
sions of twenty-liour gelatin cultures are more convenient. The 
dilution and time limit are the same as in typhoid. Some cases 
will react even in 1: 120 dilution. The reaction can be performed 
with dried blood and persists into convalescence (seven months or 
more). 

2. Malta Fever. 

Wright and Smith tested the serum of fifteen cases of Malta fever 
with the micrococcus vielitensis of Bruce, and found a strong clump 
reaction to occur (1 : 50 in most cases). On the typhoid bacillus the 
serum of these cases had no action. Sixteen cases of typhoid 
showed no reaction with Bruce's organism. The evidence in favor 
of this organism as the cause of Malta fever is strengthened by 
these facts. Wright's observations have been confirmed by Xeusser 
and others in this country. 

Curry ^ reports his experience in twenty-six cases. He used sus- 
pension of dead cocci from seven-day agar cultures in normal salt 
solution. One drop of the susj^ected blood was mixed with thirty of 
normal salt solution, and this mixture was combined with an equal 
bulk of the suspension of cocci and left to stand in tubes 7.5 cm. 
long and 3 or 4 mm. in diameter, the lower end being drawn out 
to a -fine point. Sedimentation occurs in positive cases within 
twenty-four hours. The negative cases remain turbid for days. 

3- The Bubonic Plague. 

Zabolotny ^ studied forty cases at Bombay in April, 1897, and 
found the reaction absent in tlie first week, present in 1 : 10 dilution 
in the second week, and in 1 : 50 dilution in the third or fourth week. 
He noted that the action of the infected serum seemed to deprive 
the bacilli of their capsules. In an editorial in the Arch. Russes de 
Pathologie, May 31st, 1897, it is stated that the reaction increases 
in intensity until the fourth week of the disease and then declines; 
also that it is most marked in the severest cases. Feindel {loc. cit.) 
states that in the acute pneumonic cases the reaction is absent. 

1 Jour, of Med. Research, July, 1901. 
3 Deut. med. Woch., 1897, p. 393. 



DYSENTERY. 539 



The serum reaction is not often of practical value in the diagno- 
sis of plague, because it is rather late in appearing, and because the 
diagnosis can usually be made earlier by the microscopical and cul- 
tural tests of blood withdrawn dried from a bulb. 

TUBERCULOSIS. 

(See above, page 288.) 

DYSENTERY. 

The bacillus originally discovered by Shiga, though identical in 
most respects with that isolated at Manilla by Flexner, is not the 
same in its agglutinative reactions, and neither of these strains 
agrees with the organism obtained by Bassett and Duval ' in respect 
to this reaction. Further than this Park^ has shown that normal 
serum is capable of agglutinating both the "Manilla" and the 
^* Shiga" strains in considerable dilution, while, on the other hand, 
Park has isolated a bacillus morphologically close to the colon group, 
but with agglutinative reactions like those of the "Shiga" strain. 
A good deal more work will have to be done before the agglutination 
test for the organism or organisms of acute dysentery are put upon 
a satisfactory basis for general clinical work, 

' Bassett and Duval: Am. Med., 1902, vol. iv., p. 417. 
'FsLYli: Am. Assn. of Pathol., Washington, May 12th, 1903. 



BIBLIOGRAPHr. 



It has seemed to me best to give a list only of the books which 
I have found most useful, since the general bibliography of the 
subject is now large enough to form a volume by itself. Most of 
the larger works here described contain extensive bibliographies — 
especially that by Ewing. 

Text-Books. 

1. Ewing: "Clinical Pathology of the Blood," Phila., 2d edition, 1903, 
8vo, 495 pp. (Lea Bros.). This is the newest book on the blood and the fullest 
discussion of the theoretical points connected with diseases of the blood. The 
bibliography and resume of the work of other observers contained in each 
section are admirable. The original observations of the writer are contained 
chiefly in the chapters on malaria and diphtheria. The tone of the book is ad- 
mirably sane and judicial throughout. The illustrations are poor. 

2. Ehrhch, Lazarus, Pinkus, and v. Noorden in vol. viii. of Nothnagel's 
"Specielle Pathologic und Therapie," issued between 1898 and 1901 (Wien, 
Holder & Co.) have written a series of articles on anaemia, leukaemia, and 
chlorosis, which together amount to many pages 8vo. The clinical aspects 
and therapeutics of the diseases are included. The haematology of the book is 
on the whole inferior to Ewing's, although parts of it, especially v. Noorden's 
study of chlorosis, are masterly. The articles on anaemia are interesting as 
they contain Ehrlich's latest utterances. The work is out of date in some re- 
spects owing to its characteristically Teutonic ignorance of important ^vork 
done in England and America, but it is undoubtedly the standard German 
work on the subject. 

3. Da Costa : "Clinical Haematology," Phila., 1901, 8vo, 474 pages Con- 
veniently arranged, well illustrated, not especially original. 

4. Hayem: "Du Sang," Paris, 1889, 8vo, 1035 pages (French) This val- 
uable book is the largest that I know of on the subject, and contains a mine of 
information on the morphology of the blood in health and disease, mostly 
from the author's own experience, literature being but little referred to. It 
contains a comparative anatomy of the blood and a long account of blood de- 
velopment. Unfortunately, it is dominated throughout by a theory of blood 
formation which has never gained acceptance by any other authority. It is 
very full on the subject of fibrin formation and of chlorosis. The illustrations 
are excellent. In a later work, "Lemons sur les Maladies du Sang," Paris, 
1900, 8vo, 700 pages (Masson et Cie.), Hayem has brought his previous book 
in a measure up to date, but the "Lemons" are very diffuse and wordy and 



542 BIBLIOGRAPHY. 

contain but a small fraction of the original work for which Hayem's first hook 
was so notable. 

5. V, Limbeck: " Grundriss ein. klin. Pathologic des Blutes," Jena, 1896, 
8vo, 383 pages (Fischer). The second edition of this book, which appeared 
in February, 1896, is more than twice the size of the first edition (1892) — a 
fact illustrating the rapidity of the subject's growth. It is on the whole the 
best general text-book known to me, being equally full on all parts of the 
subject, including, for example, technique (which Grawitz omits) and of the 
chemistry of the blood, which is at present the author's special interest and on 
which Hay em is meagre. The illustrations are poor and the type is trying to 
the eyes. The writer shows little personal experience with the morphology 
and micro-chemistry of the blood, and this is the weakest side of the book. A 
large part of the book is concerned Avith the physiology of the blood. 

6. Grawitz: "Klinische Pathologic des Blutes," Berlin, 1895, 8vo, 333 
pages (Enslin). Issued in April, 1896. This book is largely devoted to the 
matter indicated by the title and contains no account of blood technique, and 
only thirty pages on the normal anatomy and physiology of the blood, while 
two hundred and seventy concern the blood in disease. The arrangement of 
the book is very clear and helpful. The author's main interests are in the 
estimation of the dried residue of the blood in various diseased conditions and 
in the bacteriology of the blood, so that the book is specially full on these 
topics. The illustrations are poor. Type and paper are excellent. 

7. Coles: " The Blood: How to Examine It," etc., London, 1898 (J. and A. 
Churchill), 8vo. A clear and fairly complete account of the work of others 
upon the subject. Especially full on technique. 

These are tlie best text-books known to me on the whole subject. 
Taylor's masterly monograph, entitled " Studies in Leukaemia " and 
forming part of the volume of '' Contributions from the William 
Pepper Laboratory of Clinical Medicine" (Philadelphia, 1900), 
contains within its one hundred and seventy-eight quarto images not 
merely an unrivalled account of leukaemia but a great deal of im- 
portant matter on leucocjrtosis, anaemia, and most other haemato- 
logical topics. It is by far the best study of leukaemia known to 
me in any language. 

Treatises on Special Portions of the Subject. 

1. Keinert's " Die Zahlung der Blutkorperchen, '^ Leipzig, 1891 (Vogel), 246 
pages, is an admirable account of the avoidable and unavoidable errors in 
blood examination, and the best methods of rcducing error to a minimum. A 
number of careful examinations of the blood in health and in various diseases 
are also given ; and an outline of the scope of blood diagnosis closes the book. 

2. Turk's monograph on the " Condition of the Blood in Acute Infectious 
Disease " is an admirable resume of German and French literature on the sub- 
ject, together with a detailed study of fiftj^-two cases. Published at Wien 
and Leipzig, 1898 (Braumuller), 347 pages, 8vo. 



BIBLIOGRAPHY. 543 

3. Rieder's "Beitrage zur Kenntniss der Leukocytosis," Leipzig, 1893 
(Yogel), 220 pages, is an admirable work in all respects, although now consid- 
erably out of date. It shows, as very few of the foregoing treatises do, a 
practical acquaintance, on the author's part, with the details of blood mor- 
phology and microchemistry. A very large number of blood counts in many 
diseases are recorded. 

4. Lowitt's " Studien zur Physiol, und Pathol, des Blutes u. der Lymphe " 
(Jena, 1892 [Fisher] , 8vo, 138 pages) is mostly concerned with experiments on 
animals and intended to throw light on the theory of leucocytosis. The con- 
clusions of the book have not been generally adopted, though its facts have 
been mostly verified. 

5. Thayer and Hewetson's book, on the "Malarial Fevers of Baltimore," 
leaves nothing more to be desired in that direction. It is two hundred and 
fifteen pages long, published by the Johns Hopkins press of Baltimore in 1895. 
It contains a summary of tlie literature of the subject, an analysis of six hun- 
dred and sixteen new cases, and some admirable colored plates. It is a model 
of its kind in every respect, and an ideal for others to aim for. Essentially 
the same material is reorganized in Thayer's " Lectures on the Malarial Fevers," 
New York, 1899, Appleton. 

6. Ehrlich's " Farbenanalytische Untersuchungen " (Berlin, 1891 [Hirsch- 
wald], 137 pages) contains nine short essays by Ehrlich and three by his pu- 
pils. Considering the reputation of the writer they are at the present day 
rather disappointing reading, and contain little that is not better expressed 
elsewhere. 

7. Weiss's "Haematologische Untersuchungen" (Wien, 1896 [Prochaska] 
113 pages, Svo) contains many valuable studies on various points. 



INDEX. 



Abscess, 204, 245, 256, 260-267 

diagnostic value of blood in, 249 

felon, 265 

gum boil, 265 

of liver, 343 

of lung, 266 

of neck, 265 

of ovary, 265 

of parotid, 265 

of vulva, 265 

pelvic, 260 

perinepliritic, 265 

psoas, 265 

subpectoral, 265 

subphrenic, 267 

vaginal, 265 
Actinom3XOsis, 271 
Acute 3^ellow atrophy of liver, 339 
Addison's disease, 398 
Adenitis, 172, 306 
Alcoholism, 417 
Alkalinity of blood, 47 
Altitude, effects on blood, 74 
Amoeboid movements, 51 
Anaemia, 76 

aplastic, 146 

infantum pseudoleuksemica, 519 

of infancy, 513 

pernicious, 123 

primary, 76 

secondary or symptomatic, 78, 86 

splenic, 182 

tropical, 76 

with dilated stomach, 325 

with ulcer of stomach, 317 
Annesthesia, 253, 408 
Aneurism, 360 
Ankylostomiasis, 490 
Antitoxin (diphtheria), 210, 212 
Appendicitis, 245 

diagnosis of, 248, 252, 259 
Arthritis, 399 
Asthma, 375 

Bacteriology of the blood, 45 

in pneumonia, 187 
Basedow's disease, 396 
Beri-beri, 273 
35 



Bilharzia disease, 486 
Bleeders, 8 

Blood destruction, 405 
Bone, diseases of, 399 
Brain, diseases of, 383 
Bronchitis, 204, 373 

acute, 374 

chronic, 375 
Bronchopneumonia, 195, 204, 221 
Brownian movement, 11, 58, 79 
Bubonic plague, 271, 538 
Burns, influence on blood, 407 

Caisson disease, 386 
Cancer, 423-453 

eosinophiles in, 451 

generalized, 445 

leucocytes in, 434-452 

myelocytes in, 452 

nucleated red cells in, 427 

of abdominal organs, 445 

of breast, 430, 432, 448 

of gullet, 431. 489 

of intestine. 443 

of kidney, 446 

of lip, 448 

of liver, 345 440 

of mediastinum, 449 

of neck, 449 

of omentum, 446 

of ovary, 448 

of pancreas, 449 

of prostate, 448 

of skull, 450 

of stomach, 430, 433 

of stomach, digestion leucocyto 
sis in, 436 

of uterus, 430, 447 

of vertebrae, 449 

f)Osition of tumor and its iutlu- 
ence, 429 

qualitative changes in blood. 427 

qualitative changes in leucocvtes, 
450 

regeneiation of blood in, 425 
Cathartics, influence on blood, 326 
Cerebral liemorrhage, 385 
Cerebral tumor, 383 



546 



INDEX. 



Cliarcol-Leydeu crystals, 165 
Chlorosis, 147 

blood plates in, 153 

deformities in, 151 

diagnosis of, 153 

eosinophiles in, 152 

lymphocytes in, 152 

myelocytes in, 152 

neutrophiles in, 152 

red cells in, 148 

specific gravity, 151 

volume of blood in, 148 

white cells in, 152 
ChoLnemia, 389 
Cholangitis, 342 
Cholecystitis, 204, 342 
Cholelithiasis, 340 
Cholera, 231 

acidity of blood in, 231 

serum reaction in, 537 
Chorea 387 
Cirrhosis of liver, 332 
Coagulation in jaundice, 46 

in pernicious anaemia, 46 

in purpura, 46 

of blood, 57 
Cold, effects of, 94 
Concentration of blood, 68, 71 
Conjunctivitis, 204 
Constitutional diseases, 391 
Convulsions, effect of. 389 
Corpuscles, biconcavity, 50 

crenation, 50 

number of, 54 

red, effects of fatigue on, 56 

resistance. 47 

white, 56, 60 
Counting corpuscles, 12-24 

corpuscles (differential), 44 
Cretinism, 396 
Cyanosis, 190 
Cysticercus, 443 
Cystitis, 205 

Degeneration of corpuscles, 50, 189 

Dengue. 272 

Diabetes, 391 

Diarrhoea, 9, 328, 513 

Digestion leucocytosis in cancer, 436 

Digestive organs, diseases of, 315 

Diphtheria, 210 

Distomum haematobium, 486 

Distribution of blood, 68 

Dunham's haemocytometer, 22 

Duodenal ulcer, 321 

Dysentery, 209. 327, 504, 539 

Dyspepsia, 323 

EcHiNOCOCCus cyst, 337 
Eczema, 507 



Electric shock, 422 

Electricity, effect on blood, 47 

Emphysema, 376 

Empyema, 278 

Endocarditis, 346 

Endoglobular changes, 79 

Enteritis. 327 

Eo.sinophiles, 61, 107, 187, 191, 205 

Eosinophilia after tuberculin, 293 

compensatory, 109 

diagnostic value of. 111 

in acute and chronic skin diseases, 
108, 505 

in ankylostomiasis, 108, 480, 495 

in astiuna, 377 

in cancer, 109, 451 

in fibrinous pneumonia, 187 

in ha-matoma, 109 

in helminthiasis, 108, 486-504 

in purpura, 109 

in scarlatina, 217 

in trichinosis. 108, 496 

medicinal. 109 

phvsiological, 108 

post-febrile, 108 
Epilepsy, 383 
Erysipelas, 232 
Ervthema nodosum, 209, 506 
Ether, 253 

Fevek, influence of, 186, 197 
Fibrin, 52, 114, 188 
Filariasis, 474 
Fractures, 400 
Frambasia. 487 
Furunculosis, 203 

Gall-stone colic, 259, 341 

Gall stones, 340 

Gas poisoning. 413 

Gastric ulcer, 316 

Gastritis, acute and chronic, 322-324 

corrosive. 326 

digestion 'leucocytosis in, 324 

in infancy. 513 

with hyperacidity, 325 
Gastroenteritis. 323 
General paralysis, 388 
Glanders. 270 
Gonorrhoea, 267 
Gout, 393 

Gowers' solution, 13 
Graves' disease, 396 
Grippe, 236 

HEMATOCRIT, 28 

Haemoglobin, 30, 113 
Haemoglobinaemia, 406, 473 
Haemoglobinometers, 30-35 
Haemolysis, 405 



i 



i 



INDEX. 



547 



Hremophilia, 405 

Hayem's solution, 25 

Heart, congenital disease of, 355 

diseases of, 346-360 
Heat exhaustion, 421 
Hemorrhage, 116, 201 

blood regeneration after, 116 

chronic, 119 
Herpes zoster, 506 
Hodgkin's disease, 175, 521 
Hydatid. 337 
Hydraimia, 86 
Hydronephrosis, 373 
Hydrophobia, 272 
Hypochondriasis, 389 
Hysteria, 389 

Illuminating gas, poisoning by, 413 
Infancy, anaemias of, 513 

blood in, 510-527 

chlorosis in. 514 

hereditary syphilis in, 515 

leucocytosis in. 514 

leukaemia in, 526 

Ij'mphocytosis in, 512 

polyc3'th;emia in, 513 

rickets in, 515 
Influenza, 236 

Intestinal parasites, 488, 502 
Intestine, disease of, 326 

obstruction of, 329 
lodophilia, 42, 255 
Isotonic coeflicient. 47 

Jaundice, catarrhal, 330 

coagulation in, 331 
Justus reaction in sj'philis, 310 

Kidneys, diseases of, 360 
pyonephrosis, 373 
uraemia, 369 

Lead poisoning, 419 
Leprosy, 313 
Leucocytes, 60, 291 

degenerated. 66 

eosinophilic (see Eosinophiles), 61 

in abscess, 245 

in smallpox, 221 

iodine reaction in, 42, 255 

mononuclear neutrophilic, 46, 65 

normal percentages of, 63 

origin of, 62 

pol^ymorphonuclear, 60 

"stimulation forms," 66 

transitional neutrophiles, 66 
Leucocytosis, absence of, 104 

after exercise, massage, and 
baths, 94 

cell changes in, 102 



Leucocytosis, definition, 88 

diagnosric value of, 97 

diurnal, 90 

experimental, 101 

inflammatory, 97 

in malignant disease, 100 

in new-born infants, 92 

in pneumonia. 189 

in pregnancy, 92 

pathological, 96 

physiological, 90 

post-hemorrhagic, 96 

post-partum, 93 

terminal, 96 

therapeutic, 101 

toxic, 100 
Leucopenia, 104 
Leukaemia, 155-174, 526 

in infancy, 526 

remissions in, 166, 173 
Lipaemia, 115 
Liver abscess, 343 

cirrhosis of, 332 
Lung, diseases of, 373 
Lymphaemia, 166 
Lymphatic leukeemia, 166 
Lymphocj^tes, 61 
Lymphocytosis, 105 

in hereditar}- s^'philis. 106 

in infancy, 512 

in pertussis, 106, 221 

in splenic tumors, 106 

in thyroidism, 106 

Macrocytes, 85, 129 

Malaria, 462-473 

and typhoid, 208, 472 
parasites of, 462 
pigmented parasites, 464 
segmentinsT parasites, 467 

Malta fever, 269, 538 

Mast cells, 62, 165 

Measles, 218 

Megaloblasts, 83, 132, 134 

Melanamia, 116 

Meningitis, 209, 284, 303 
tuberculous, 303 

Mental diseases, 390 

Methaemoglobina?mia, 408 

Microblasts, 83 

Microcytes, 79 

Muller's blood dust, 58 

Mumps, 220 

Myelocytes, 64, 111, 161, 189, 223. 452 

Myeloid leuka^nia, 156 

Myxcrdema. 394 

ISTarcosis, eifect on l)lood, 253 
Necrobiosis of red cells, 78 
Nephritis, 361 



548 



INDEX. 



JSTeplirolitl'iiasis, 37 1 

Nervous system, diseases of, 381-391 

Neurasthenia, 389 

Neuritis, 381 

Newton's rings, lo 

Normoblasts, 82, 157, 189 

Nucleated red cells, 82, 189, 427 

Obesity, 391 

Obstruction (intestinal). 329 
Oliver's instruments, 25, 32 
Osteomalacia, 400 
Osteomyelitis, 265 
Otitis media, 263 

Panckeas, diseases of, 345 
Parasites, animal, diseases due to, 
474, 502 

filarial, 474 

intestinal, 488, 502 

malarial, 462 
Parotitis, 220, 204 
Paroxysmal lia;moglobina'mia, 407 
Parturition, blood on and after, 93 
Pericarditis, 204, 282 

tuberculous, 306 
Periostitis, 204 
Peritonitis, 280 

pelvic, 260 

tubeiculous, 301 
Pernicious amrmia, 123 

anaemia, diagnosis of, 140 

ansemia, gross appearance of 
blood, 123 

anaemia, haemoglobin in, 128 

anaemia in infancy, 520 

aUcTmia, nucleated red cells in, 
132 

anaemia, prognosis in. 143 

anaemia, red cells in, 124-135 

anaemia, remissions in, 138 

anaemia, white cells in, 135 

malaria (see Malaria) 
Pertussis, 106, 220 
Phosphorus poisoning, 339 
Phthisis, 291 

Pipettes, use and care of, 13 
Plague, bubonic, 271, 538 
Platelets, 51, 57 
Plethora, 70 
Pleurisy, purulent, 278 

serous, 275 

tuberculous, 306 
Plumbism, 419 
Pneumonia, 187, 204 

bacteriology of blood, 187 

broncho-, 195 
Poikilocytosis, 78 
Poisoning, by antip3'retics, 410-412 

by arsenic, 417 



Poisoning, by belladonna, 416 

by carbolic acid, 417 

by carbonic oxide, 412 

by chloral, 416 

bv corrosive sublimate, 416 

by ether, 253, 408 

bv illuminating gas, 412 

by lead, 419 

by mercury, 417 

by opium, 415 

by phosphorus. 339 

l)y potassium chlorate, 408 

by ptomains. 417 

by pyrogallic acid. 412 

by snake venom, 406 

by tansy, 415 
Polychromatophilia, 80 
i\)lycytha-mia. 70 
Pregnancy, 92 

Puerperium. leucocytes in, 93 
Purpura, 403 
Pus tul)e, 260 
Pyelonephritis, 371 

Rabies, 272 

Regeneration of blood, 117 
Relapsing fever. 274. 481 
Rheumatism, 224 
Rickets. 401 
Rotheln, 219 
Rouleaux formation, 49 

Sarcoma, 452 

Scarlatina, 215 

Scurvy, 404 

Septicaemia. 237 

Serous membranes, diseases of, 275 

Serum diagnosis. 528 

diagnosis of bubonic plague, 538 
diagnosis of cholera, 537 
diagnosis of dysentery, 539 
diagnosis of 3ialta fever, 538 
diagnosis of typhoid, 529 

Skin, dtseases of, 503-509 

Slides, preparation of,, 9, 41 

Smallpox, 221 

Snake poison, 406 

Solids of the blood, 48 

Specilic gravity of blood, 37 

Splenectom3^ i81 

Splenic anaemia, 182 
extract. 174 

m3Tloid leukaemia (see Leukae- 
mia) 

Spotted fever. 485 

Staining blood films, 41-44 

Strongjdoides intestinalis, 502 

Suffocation by smoke, 416 

Sunstroke. 421 

Suro-ical diseases, blood in, 253 



INDEX. 



549 



Surgical, kidney, 371 
Syphilis, 308, 379 

TAENIA, 504 

Tetanus, 272 

Tetany, 387 

Thoma-Zeiss' instruments, 13, 15 

Thrombosis, 203 

Thyroid extract, effects of, 394 

Toisson's solution, 13 

Tonsillitis, 234 

Toxicity of blood, 188 

Trichinosis, 497 

Tricocephalus, 504 

Trypanosomiasis, 487 

Tuberculosis, 288-309 

acute miliary, 297 

fibrin in, 289 

glandular, 306 

leucocytes in, 291 

of bone, 294 

of meninges, 303 



Tuberculosis, of pericardium, 306 

of peritoneum, 301 
Typhoid fever, 196 

fever, serum reaction in. 529 
Typhus, 269 

Uncixaeiasis, 490 
Uraemia, 369 
Urethritis, 204, 267 
Uric acid in blood, 393 

VxVCCINATION, 221 

Vaccinia, 221 
Varicella, 223 
Variola, 221 

Whooping-cough, 106, 220 

Yellow fever, 268 

Zappert's counting-chamber, 21 



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